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Scientific Overview Research Interest Summary Principal Investigators    Yuri Bushkin, Ph.D.
   Theresa Chang, Ph.D.
   Neeraj Chauhan, Ph.D.
   Véronique Dartois, Ph.D.
   Thomas Dick, Ph.D.
   Karl Drlica, Ph.D.
   David Dubnau, Ph.D.
   Eliseo A. Eugenin, Ph.D.
   Marila Gennaro, M.D.
   Fred Kramer, Ph.D.
   Barry Kreiswirth, Ph.D.
   Min Lu, Ph.D.
   Leonard Mindich, Ph.D.
   Arkady Mustaev, Ph.D.
   Jyothi Nagajyothi, Ph.D.
   David Perlin, Ph.D.
   Abraham Pinter, Ph.D.
   Marcela Rodriguez, Ph.D.
   Selvakumar Subbian, Ph.D.
   Sanjay Tyagi, Ph.D.
   Christopher Vinnard, M.D.
   Chaoyang Xue, Ph.D.
   Xilin Zhao, Ph.D.

   Research Faculty
   Liang Chen, Ph.D.
   Eugenie Dubnau, Ph.D.
   Jeanette Hahn, Ph.D.
   Salvatore Marras, Ph.D.
   Lanbo Shi, Ph.D.
   Yanan Zhao, Ph.D.

Emeritus Faculty Recent Publications
David Perlin, Ph.D.
      Executive Director and Professor

Research Summary  |  Recent Publications  |  C.V.

Public Health Research Institute Center
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3200
e-mail: perlinds@njms.rutgers.edu


 Lab Members  Visiting Scientists
 Dr. Yanan Zhao  Dr. Soo-Hyun Kim
 Dr. Cristina Jiménez-Ortigosa  Ms. Milena Kordalewska
 Dr. Kelley Healey  
 Dr. Erika Shor  
 Dr. Enriko Dolgov  
 Dr. Yevgeniy Senin  
 Ms. Padmaja Paderu  
 Mr. Guillaume Delmas  

Research Summary

The Perlin lab is interested in mechanisms of antifungal drug resistance, rapid detection of drug resistant bloodstream and respiratory pathogens in high-risk patients, drug discovery against multidrug resistant bacterial infections, and the application of small animal models for respiratory pathogens.

Mechanisms of antifungal drug resistance. Fungal infections are a significant cause of morbidity and mortality in severely ill patients. The widespread use of antifungal agents has resulted in selection of less susceptible fungal species, as well as the emergence of resistance in susceptible species. Echinocandins are important antifungal agents for the treatment of patients with Candida infections. These drugs target the fungal cell wall by blocking b-1,3-D-glucan synthase, but therapeutic failures are increasingly reported, especially with C. glabrata. We have demonstrated that amino acid substitutions in the catalytic Fks subunits of glucan synthase account for resistance in clinical isolates of Candida spp. To better understand echinocandin resistance, cellular factors are being examined in in vitro and in vivo models for their role in emergence of fks-mediated echinocandin resistance. Specifically, compensatory cell wall stress responses, DNA repair, azole resistance, and novel genes/pathways are being profiled. This work exploits engineered isogenic mutant strains and genetically matched susceptible and fks-resistant clinical isolates of C. glabrata. These latter isolates will be profiled for changes in the genome and transcriptome to assess the importance of known mechanisms and elucidate new genetic mechanism underlying resistance emergence. It is anticipated that this information will provide important new insights and potential intervention strategies to overcome or prevent the emergence of echinocandin resistance. The Perlin Lab serves as an Astellas-supported Global Reference Center for echinocandin resistance

We are also studying mechanisms of triazole resistance in chronic Aspergillus fumigatus infections in collaboration with Dr. David Denning, Director of the National Aspergillosis Center, Manchester, UK. We have characterized a wide array of mutations in the Cyp51A gene, which confers differential resistance to itraconazole, voriconazole and posaconazole. The objective of this work is to evaluate trends in resistance and develop approaches for rapid diagnosis of drug resistant infections and explore drug/dosing regimens that overcome resistance. This work is funded by NIH/NIAID grant 1R01AI109025 and a grant from Astellas.

Rapid detection of respiratory and bloodstream infections and associated resistance markers. Blood stream infections (BSIs) are a significant cause of morbidity and mortality in the USA. Early antimicrobial therapy is critical to a favorable outcome for patients with BSIs. Current diagnostic methods can take from 24 hours up to a week for positive pathogen identification and even longer for drug susceptibility. Reducing the time period from specimen collection to species identification and antimicrobial susceptibility is essential for improving outcome for patients. We are developing next-generation nucleic acid PCR- and RNA-based molecular beacon platforms for rapid identification of bacterial and fungal pathogens, and associated drug resistance in selected organisms including KPC, MRSA, VRE, C. difficile, Candida spp. and Aspergillus spp. The new diagnostic tools are being validated in prospective clinical validation studies with clinical partners.

Detection of unculturable cryptic infections causing chronic diseases is a major concern for medical mycology. A. fumigatus causes a wide spectrum of diseases including allergic syndromes, chronic pulmonary aspergillosis and acute invasive aspergillosis. The rapid increase in triazole resistant Aspergillus infections is a growing public health and patient management concern. Our goal is to elucidate key microbial factors influencing resistance associated with chronic and acute Aspergillus infections following initiation of therapy. Bronchial alveolar lavages and other respiratory fluids are being evaluated from patients with documented chronic and acute Aspergillus infections before and after initiation of antifungal therapy. An Aspergillus PCR and a novel expression profiling method is being used to detect the presence of A. fumigatus; and real-time PCR assays using molecular beacon technology is being applied to recognize well-defined resistance markers in cyp51A gene. This work will advance our understanding of the importance of triazole resistance in the management of patients with chronic Aspergillus and allergic disease requiring prolonged antifungal therapy. This work is supported by NIH/NIAID grant 1R21AI103636.

Drug discovery against multidrug resistant bacteria causing both systemic and wound Infections

Center of Excellence in Translational research (CETR) to develop therapeutic countermeasures to high-threat bacterial agents.An epidemic of multidrug-resistant (MDR) bacterial infections plagues global and U.S. healthcare, and with few new antibiotics making it to market from a diminished pipeline, there is an unmet medical need for new therapeutics to treat drug-resistant infections. Furthermore, effective therapies are urgently needed to address ongoing public health and biosecurity concerns that high-threat select agent bacteria can be engineered to become resistant to currently available antibiotics. The goal of the Rutgers CETR is to help develop a new generation of antibiotics against known MDR bacteria. The CETR is a collaborative public-private partnership involving senior investigators at Rutgers University, Rockefeller University and Cubist Pharmaceuticals. It will serve to jump-start the discovery of novel antibiotics by joining together highly creative senior researchers and providing critical core resources to turn highly promising early concept molecules into potential therapeutics suitable for clinical evaluation. The CETR will examine known, well established, and novel therapeutic targets, and it will facilitate target validation, chemical lead identification, structure-activity relationship analysis, pharmacokinetics and therapeutic efficacy in animal models. The goal is to develop optimized chemical lead compounds that are suitable antibiotic candidates for preclinical evaluation. Critical factors for success include the strength of highly accomplished project and core leaders, a comprehensive and highly integrated infrastructure of support cores for lead compound optimization and validation, and access to the Rutgers Regional Biocontainment Laboratory (RBL), an NIH designated national research center for high-threat agents. Finally, the CETR leadership group is highly experienced in executing product-oriented translational research and a Scientific Advisory Committee comprised of veteran members of PhRMA and academia will guide them. This program is supported by NIH/NIAID grant 1U19AI109713.

Evaluation of carbohydrate-derived fulvic acid (CHD-FA) in preventing the development of multidrug resistant bacterial and fungal infections in traumatic wounds. The objective of this study is to demonstrate the potent antimicrobial properties of carbohydrate-derived fulvic acid (CHD-FA) against a broad collection of drug-sensitive and multi-drug resistant bacterial and fungal pathogens commonly associated with wound infections, and assess the relative efficacy of CHD-FA against induced wound infections in in vivo animal models. CHD-FA possess broad-spectrum antimicrobial behavior and is highly active on a wide array of multi drug resistant Gram positive and Gram negative bacteria, as well as common fungal pathogens. CHD-FA also shows anti-inflammatory properties and has properties that are ideal for field deployment as a broad-spectrum topical antimicrobial. Given its novel mechanism of action, activity against MDR bacteria and fungi, and anti-inflammatory activity, the early use of CHD-FA may present an advantage over existing agents to prevent serious infections following traumatic injuries including skin/soft tissue and burns. This work is supported by Department of Defense grant (CDMRP) DM110303.

Animal models of infection. We are actively engaged in developing and running BSL2/BSL3 small animal infection models for bacterial, fungal and viral pathogens.

Provide small animal infection models for ESKAPE, TB and select agent bacterial pathogens to evaluate lead compounds. The models include skin and soft tissue infection (SSTI) models (ESKAPE pathogens), pneumonia (ESKAPE and Select Agents) and systemic bacteremia (ESKAPE) models. For M.tb, acute and chronic infection models are used to assess leads at different stages of M.tb infection in rodents and rabbits. We perform measurements of host response and bacterial burden analyses at both the molecular and cellular levels. Assays include wound closure measurements, histopathologic assessment of wound healing, host wound healing pathway RNA profiling, reduction of bacterial burden and in vivo imaging. All the services provided can be performed under high-level BSL3 biocontainment in the Rutgers RBL, which served as the Small Animal Core for the Northeast Biodefense Center’s (NIH RCE Region II) for the past 12 years. An important part of the ongoing RBL function is to maintain small animal models of select agents, including murine and other small animal models of infection with Mycobacterium tuberculosis (MDR/XDR- TB), Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia spp., avian and pandemic flu. In the past eight years, our group has logged >1.5 million animal days of BSL3 infection agents, including >650,000 with tier 1 select agents. We have run more than 20 vaccine studies with these agents during this period.

Recent Publications

Zhao Y, Paderu P, Delmas G, Dolgov E, Lee MH, Senter M, Park S, Leivers S, Perlin DS (2015) Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens. J Trauma Acute Care Surg 79: S121-129. PMI: 26406424

Solorzano A, Foni E, Cordoba L, Baratelli M, Razzuoli E, Bilato D, Martin Del Burgo MA, Perlin DS, Martinez J, Martinez-Orellana P, Fraile L, Chiapponi C, Amadori M, Del Real G, Montoya M (2015) Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine. J Virol 89: 11190-11202. PMI: 26311894

Shor E, Perlin DS (2015) Coping with stress and the emergence of multidrug resistance in fungi. PLoS Pathog 11: e1004668. PMI: 25790300

Perlin DS, Shor E, Zhao Y (2015) Update on Antifungal Drug Resistance. Curr Clin Microbiol Rep 2: 84-95. PMI: 26120512

Perlin DS (2015) Echinocandin Resistance in Candida. Clin Infect Dis 61 Suppl 6: S612-617. PMI: 26567278

Perlin DS (2015) Mechanisms of echinocandin antifungal drug resistance. Ann N Y Acad Sci 1354: 1-11. PMI: 26190298

Perlin DS (2015) Echinocandin Resistance in Candida. Clin Infect Dis 61 Suppl 6: S612-617. PMI: 26567278

Jensen RH, Astvad KM, Silva LV, Sanglard D, Jorgensen R, Nielsen KF, Mathiasen EG, Doroudian G, Perlin DS, Arendrup MC (2015) Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations. J Antimicrob Chemother 70: 2551-2555. PMI: 26017038

Ioannou P, Andrianaki A, Akoumianaki T, Kyrmizi I, Albert N, Perlin D, Samonis G, Kontoyiannis DP, Chamilos G (2015) Albumin enhances caspofungin activity against Aspergillus species by facilitating drug delivery to germinating hyphae. Antimicrob Agents Chemother. PMI: 26643329

Espinel-Ingroff A, Alvarez-Fernandez M, Canton E, Carver PL, Chen SC, Eschenauer G, Getsinger DL, Gonzalez GM, Govender NP, Grancini A, Hanson KE, Kidd SE, Klinker K, Kubin CJ, Kus JV, Lockhart SR, Meletiadis J, Morris AJ, Pelaez T, Quindos G, Rodriguez-Iglesias M, Sanchez-Reus F, Shoham S, Wengenack NL, Borrell Sole N, Echeverria J, Esperalba J, Gomez GdlPE, Garcia Garcia I, Linares MJ, Marco F, Merino P, Peman J, Perez Del Molino L, Rosello Mayans E, Rubio Calvo C, Ruiz Perez de Pipaon M, Yague G, Garcia-Effron G, Guinea J, Perlin DS, Sanguinetti M, Shields R, Turnidge J (2015) Multicenter Study of Epidemiological Cutoff Values and Detection of Resistance in Candida spp. to Anidulafungin, Caspofungin, and Micafungin Using the Sensititre YeastOne Colorimetric Method. Antimicrob Agents Chemother 59: 6725-6732. PMI: 26282428

Dudiuk C, Gamarra S, Jimenez-Ortigosa C, Leonardelli F, Macedo D, Perlin DS, Garcia-Effron G (2015) Quick Detection of FKS1 Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans. J Clin Microbiol 53: 2037-2041. PMI: 25878347

Doman M, Kovacs R, Perlin DS, Kardos G, Gesztelyi R, Juhasz B, Bozo A, Majoros L (2015) Dose escalation studies with caspofungin against Candida glabrata. J Med Microbiol 64: 998-1007. PMI: 26296340

Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS (2015) Mechanisms of Antifungal Drug Resistance. Cold Spring Harb Perspect Med 5: a019752. PMI: 25384768

Zhao Y, Kontoyiannis DP, Roilides E, Walsh TJ, Perlin DS (2014) Reply to "not over yet: fungal infections following methyl prednisolone injections smoulder on". J Clin Microbiol 52: 3508. PMI: 25143421

Zhao Y, Kontoyiannis DP, Roilides E, Walsh TJ, Perlin DS (2014) Reply to "detection of multiple fungal species in blood samples by real-time PCR: an interpretative challenge". J Clin Microbiol 52: 3517. PMI: 25143425

Zhao Y, Armeanu E, DiVerniero R, Lewis TA, Dobson RC, Kontoyiannis DP, Roilides E, Walsh TJ, Perlin DS (2014) Fungal DNA detected in blood samples of patients who received contaminated methylprednisolone injections reveals increased complexity of causative agents. J Clin Microbiol 52: 2212-2215. PMI: 24719442

Staab JF, Neofytos D, Rhee P, Jimenez-Ortigosa C, Zhang SX, Perlin DS, Marr KA (2014) Target enzyme mutations confer differential echinocandin susceptibilities in Candida kefyr. Antimicrob Agents Chemother. PMI: 24982083

Simitsopoulou M, Walsh TJ, Kyrpitzi D, Petraitis V, Kontoyiannis DP, Perlin DS, Roilides E (2014) Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum. Med Mycol. PMI: 25056961

Perlin DV, Sapozhnikov AD, Darenkov SP, Efremov EA (2014) [Treatment of exstrophy of bladder in adults]. Urologiia: 121-124. PMI: 25807774

Perlin DS (2014) Echinocandin resistance, susceptibility testing and prophylaxis: implications for patient management. Drugs 74: 1573-1585. PMI: 25255923

Perlin DS (2014) Echinocandin resistance, susceptibility testing and prophylaxis: implications for patient management. Drugs 74: 1573-1585. PMI: 25255923

Monteiro AA, Pires RN, Baethgen LF, Carneiro LC, Tavares RG, Caierao J, Park S, Perlin DS, Rodrigues Filho EM, Pasqualotto AC (2014) Discrepancies among three laboratory methods for Clostridium difficile detection and a proposal for their optimal use. FEMS Microbiol Lett 350: 133-137. PMI: 24236508

Krel M, Petraitis V, Petraitiene R, Jain MR, Zhao Y, Li H, Walsh TJ, Perlin DS (2014) Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic response. Antimicrob Agents Chemother 58: 3373-3378. PMI: 24687510

Kovacs R, Gesztelyi R, Perlin DS, Kardos G, Doman M, Berenyi R, Majoros L (2014) Killing rates for caspofungin against Candida albicans after brief and continuous caspofungin exposure in the presence and absence of serum. Mycopathologia 178: 197-206. PMI: 25118874

Katragkou A, Pana ZD, Perlin DS, Kontoyiannis DP, Walsh TJ, Roilides E (2014) Exserohilum infections: review of 48 cases before the 2012 United States outbreak. Med Mycol 52: 376-386. PMI: 24682112

Jimenez-Ortigosa C, Paderu P, Motyl MR, Perlin DS (2014) Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida Species and Aspergillus species isolates. Antimicrob Agents Chemother 58: 1248-1251. PMI: 24323472

Jensen RH, Justesen US, Rewes A, Perlin DS, Arendrup MC (2014) Echinocandin Failure Case Due to a Previously Unreported FKS1 Mutation in Candida krusei. Antimicrob Agents Chemother 58: 3550-3552. PMI: 24687511

Gamaletsou MN, Daikos GL, Walsh TJ, Perlin DS, Ortigosa CJ, Psaroulaki A, Pagoni M, Argyropoulou A, Nepka M, Perivolioti E, Kotsopoulou M, Perloretzou S, Marangos M, Kofteridis D, Grammatikou M, Goukos D, Petrikkos G, Sipsas NV (2014) Breakthrough candidaemia caused by phenotypically susceptible Candida spp. in patients with haematological malignancies does not correlate with established interpretive breakpoints. Int J Antimicrob Agents. PMI: 25108876

Farmakiotis D, Shirazi F, Zhao Y, Saad PJ, Albert ND, Roilides E, Walsh TJ, Perlin DS, Kontoyiannis DP (2014) Methylprednisolone Enhances the Growth of Exserohilum rostratum In Vitro, Attenuates Spontaneous Apoptosis, and Increases Mortality Rates in Immunocompetent Drosophila Flies. J Infect Dis. PMI: 24837401

Dudiuk C, Gamarra S, Leonardeli F, Jimenez-Ortigosa C, Vitale RG, Afeltra J, Perlin DS, Garcia-Effron G (2014) Set of classical PCRs for detection of mutations in Candida glabrata FKS genes linked with echinocandin resistance. J Clin Microbiol 52: 2609-2614. PMI: 24829248

Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS (2014) Mechanisms of Antifungal Drug Resistance. Cold Spring Harb Perspect Med. PMI: 25384768

Constante CC, Monteiro AA, Alves SH, Carneiro LC, Machado MM, Severo LC, Park S, Perlin DS, Pasqualotto AC (2014) Different risk factors for candidemia occur for Candida species belonging to the C. parapsilosis complex. Med Mycol 52: 403-406. PMI: 24782105

Clancy CJ, Hao B, Shields RK, Chen L, Perlin DS, Kreiswirth BN, Nguyen MH (2014) Doripenem, Gentamicin, and Colistin, Alone and in Combinations, against Gentamicin-Susceptible, KPC-Producing Klebsiella pneumoniae Strains with Various ompK36 Genotypes. Antimicrob Agents Chemother 58: 3521-3525. PMI: 24566172

Bizerra FC, Jimenez-Ortigosa C, Souza AC, Breda GL, Queiroz-Telles F, Perlin DS, Colombo AL (2014) Breakthrough candidemia due to multidrug-resistant Candida glabrata during prophylaxis with a low dose of micafungin. Antimicrob Agents Chemother 58: 2438-2440. PMI: 24468776

Arendrup MC, Perlin DS (2014) Echinocandin resistance: an emerging clinical problem? Curr Opin Infect Dis 27: 484-492. PMI: 25304391

Arendrup MC, Perlin DS (2014) Echinocandin resistance: an emerging clinical problem? Curr Opin Infect Dis 27: 484-492. PMI: 25304391

Zhao Y, Stensvold CR, Perlin DS, Arendrup MC (2013) Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases. J Antimicrob Chemother 68: 1497-1504. PMI: 23463213

Zhao Y, Petraitiene R, Walsh TJ, Perlin DS (2013) A real-time PCR assay for rapid detection and quantification of Exserohilum rostratum, a causative pathogen of fungal meningitis associated with injection of contaminated methylprednisolone. J Clin Microbiol 51: 1034-1036. PMI: 23303500

Zhao Y, Perlin DS (2013) Quantitative detection of Aspergillus spp. by real-time nucleic acid sequence-based amplification. Methods Mol Biol 968: 83-92. PMI: 23296887

Vella A, De Carolis E, Vaccaro L, Posteraro P, Perlin DS, Kostrzewa M, Posteraro B, Sanguinetti M (2013) Rapid antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. J Clin Microbiol 51: 2964-2969. PMI: 23824764

Pratt A, Garcia-Effron G, Zhao Y, Park S, Mustaev A, Pillai S, Perlin DS (2013) Evaluation of fungal-specific fluorescent labeled echinocandin probes as diagnostic adjuncts. Med Mycol 51: 103-107. PMI: 22587729

Kuboi S, Ishimaru T, Tamada S, Bernard EM, Perlin DS, Armstrong D (2013) Molecular characterization of AfuFleA, an L-fucose-specific lectin from Aspergillus fumigatus. J Infect Chemother 19: 1021-1028. PMI: 23695231

Kontoyiannis DP, Perlin DS, Roilides E, Walsh TJ (2013) What can we learn and what do we need to know amidst the iatrogenic outbreak of Exserohilum rostratum meningitis? Clin Infect Dis 57: 853-859. PMI: 23650291

Jonsson CB, Cole KS, Roy CJ, Perlin DS, Byrne G (2013) Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents. J Bioterror Biodef Suppl 3: 12634. PMI: 24900945

Jimenez-Ortigosa C, Paderu P, Motyl MR, Perlin DS (2013) Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin resistant Candida spp. and Aspergillus spp. isolates. Antimicrob Agents Chemother. PMI: 24323472

Huong DT, Zhao Y, Nguyet NT, Loan TT, Binh NT, Thinh NV, Hanh NT, Perez-Perez GI, Perlin DS (2013) Candida krusei colonization in patients with gastrointestinal diseases. Med Mycol 51: 884-887. PMI: 23815437

Hong JH, Clancy CJ, Cheng S, Shields RK, Chen L, Doi Y, Zhao Y, Perlin DS, Kreiswirth BN, Nguyen MH (2013) Characterization of porin expression in Klebsiella pneumoniae Carbapenemase (KPC)-producing K. pneumoniae identifies isolates most susceptible to the combination of colistin and carbapenems. Antimicrob Agents Chemother 57: 2147-2153. PMI: 23459476

Datta K, Rhee P, Byrnes E, 3rd, Garcia-Effron G, Perlin DS, Staab JF, Marr KA (2013) Isavuconazole activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, emerging fungal pathogens with reduced azole susceptibility. J Clin Microbiol 51: 3090-3093. PMI: 23804388

Clancy CJ, Chen L, Shields RK, Zhao Y, Cheng S, Chavda KD, Hao B, Hong JH, Doi Y, Kwak EJ, Silveira FP, Abdel-Massih R, Bogdanovich T, Humar A, Perlin DS, Kreiswirth BN, Hong Nguyen M (2013) Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients. Am J Transplant 13: 2619-2633. PMI: 24011185

Clancy CJ, Chen L, Hong JH, Cheng S, Hao B, Shields RK, Farrell AN, Doi Y, Zhao Y, Perlin DS, Kreiswirth BN, Nguyen MH (2013) Mutations of the ompK36 porin gene and promoter impact responses of sequence type 258, KPC-2-producing Klebsiella pneumoniae strains to doripenem and doripenem-colistin. Antimicrob Agents Chemother 57: 5258-5265. PMI: 23939888

Campoli P, Perlin DS, Kristof AS, White TC, Filler SG, Sheppard DC (2013) Pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis. J Infect Dis 208: 1717-1728. PMI: 23908482

Astvad KM, Perlin DS, Johansen HK, Jensen RH, Arendrup MC (2013) Evaluation of caspofungin susceptibility testing by the new Vitek 2 AST-YS06 yeast card using a unique collection of FKS wild-type and hot spot mutant isolates, including the five most common candida species. Antimicrob Agents Chemother 57: 177-182. PMI: 23089746

Alexander BD, Johnson MD, Pfeiffer CD, Jimenez-Ortigosa C, Catania J, Booker R, Castanheira M, Messer SA, Perlin DS, Pfaller MA (2013) Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 56: 1724-1732. PMI: 23487382

Alastruey-Izquierdo A, Mandelblat M, Ben Ami R, Perlin DS, Segal E (2013) Multilocus sequence typing of Candida albicans isolates from candidemia and superficial candidiasis in Israel. Med Mycol 51: 755-758. PMI: 23521555

Zhao Y, Paderu P, Park S, Dukhan A, Senter M, Perlin DS (2012) Expression turnover profiling to monitor the antifungal activities of amphotericin B, voriconazole and micafungin against Aspergillus fumigatus. Antimicrob Agents Chemother. PMI: 22314535

Garcia-Effron G, Canton E, Peman J, Dilger A, Roma E, Perlin DS (2012) Epidemiology and echinocandin susceptibility of Candida parapsilosis sensu lato species isolated from bloodstream infections at a Spanish university hospital. J Antimicrob Chemother 67: 2739-2748. PMI: 22868644

Wang Y, Liu TB, Delmas G, Park S, Perlin D, Xue C (2011) Two major inositol transporters and their role in cryptococcal virulence. Eukaryot Cell 10: 618-628. PMI: 21398509

Slater JL, Howard SJ, Sharp A, Goodwin J, Gregson LM, Alastruey-Izquierdo A, Arendrup MC, Warn PA, Perlin DS, Hope WW (2011) Disseminated Candidiasis caused by Candida albicans with amino acid substitutions in Fks1 at position Ser645 cannot be successfully treated with micafungin. Antimicrob Agents Chemother 55: 3075-3083. PMI: 21502627

Pfaller MA, Diekema DJ, Andes D, Arendrup MC, Brown SD, Lockhart SR, Motyl M, Perlin DS (2011) Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 14: 164-176. PMI: 21353623

Perlin DS (2011) Echinocandin-Resistant Candida: Molecular Methods and Phenotypes. Curr Fungal Infect Rep 5: 113-119. PMI: 0

Perlin DS (2011) Current perspectives on echinocandin class drugs. Future Microbiol 6: 441-457. PMI: 21526945

Hauser PM, Bille J, Lass-Florl C, Geltner C, Feldmesser M, Levi M, Patel H, Muggia V, Alexander B, Hughes M, Follett SA, Cui X, Leung F, Morgan G, Moody A, Perlin DS, Denning DW (2011) Multicenter, prospective clinical evaluation of respiratory samples from subjects at risk for Pneumocystis jirovecii infection by use of a commercial real-time PCR assay. J Clin Microbiol 49: 1872-1878. PMI: 21367988

Garcia-Effron G, Park S, Perlin DS (2011) Improved detection of Candida sp. fks hot spot mutants by using the method of the CLSI M27-A3 document with the addition of bovine serum albumin. Antimicrob Agents Chemother 55: 2245-2255. PMI: 21383097

Garcia-Effron G, Canton E, Peman J, Dilger A, Roma E, Perlin DS (2011) Assessment of two new molecular methods for identification of Candida parapsilosis sensu lato species. J Clin Microbiol 49: 3257-3261. PMI: 21795509

Endimiani A, Hujer KM, Hujer AM, Kurz S, Jacobs MR, Perlin DS, Bonomo RA (2011) Are we ready for novel detection methods to treat respiratory pathogens in hospital-acquired pneumonia? Clin Infect Dis 52 Suppl 4: S373-383. PMI: 21460299

Denning DW, Perlin DS (2011) Azole resistance in Aspergillus: a growing public health menace. Future Microbiol 6: 1229-1232. PMI: 22082283

Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Moore CB, Bowyer P, Perlin DS (2011) High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 52: 1123-1129. PMI: 21467016

Cagas SE, Jain MR, Li H, Perlin DS (2011) The proteomic signature of Aspergillus fumigatus during early development. Mol Cell Proteomics 10: M111 010108. PMI: 21825280

Cagas SE, Jain MR, Li H, Perlin DS (2011) Profiling the Aspergillus fumigatus proteome in response to caspofungin. Antimicrob Agents Chemother 55: 146-154. PMI: 20974863

Ben-Ami R, Garcia-Effron G, Lewis RE, Gamarra S, Leventakos K, Perlin DS, Kontoyiannis DP (2011) Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance. J Infect Dis 204: 626-635. PMI: 21791665

Arendrup MC, Rodriguez-Tudela JL, Park S, Garcia-Effron G, Delmas G, Cuenca-Estrella M, Gomez-Lopez A, Perlin DS (2011) Echinocandin susceptibility testing of Candida spp. Using EUCAST EDef 7.1 and CLSI M27-A3 standard procedures: analysis of the influence of bovine serum albumin supplementation, storage time, and drug lots. Antimicrob Agents Chemother 55: 1580-1587. PMI: 21245440

Arendrup MC, Park S, Brown S, Pfaller M, Perlin DS (2011) Evaluation of CLSI M44-A2 disk diffusion and associated breakpoint testing of caspofungin and micafungin using a well-characterized panel of wild-type and fks hot spot mutant Candida isolates. Antimicrob Agents Chemother 55: 1891-1895. PMI: 21357293

Zhao Y, Park S, Warn P, Shrief R, Harrison E, Perlin DS (2010) Detection of Aspergillus fumigatus in a rat model of invasive pulmonary aspergillosis by real-time nucleic acid sequence-based amplification. J Clin Microbiol 48: 1378-1383. PMI: 20129972

Zhang YQ, Gamarra S, Garcia-Effron G, Park S, Perlin DS, Rao R (2010) Requirement for ergosterol in V-ATPase function underlies antifungal activity of azole drugs. PLoS Pathog 6: e1000939. PMI: 20532216

Wang YP, Liu F, He HW, Han YX, Peng ZG, Li BW, You XF, Song DQ, Li ZR, Yu LY, Cen S, Hong B, Sun CH, Zhao LX, Kreiswirth B, Perlin D, Shao RG, Jiang JD (2010) Heat stress cognate 70 host protein as a potential drug target against drug resistance in hepatitis B virus. Antimicrob Agents Chemother 54: 2070-2077. PMI: 20176893

Tuohy MJ, Reja V, Park S, Perlin DS, Wnek M, Procop GW, Yen-Lieberman B (2010) Use of a high-resolution melt assay to characterize codon 54 of the cyp51A gene of Aspergillus fumigatus on a Rotor-Gene 6000 instrument. Antimicrob Agents Chemother 54: 2248-2251. PMI: 20194699

Rodriguez-Tudela JL, Gomez-Lopez A, Arendrup MC, Garcia-Effron G, Perlin DS, Lass-Florl C, Cuenca-Estrella M (2010) Comparison of caspofungin MICs by means of EUCAST method EDef 7.1 using two different concentrations of glucose. Antimicrob Agents Chemother 54: 3056-3057. PMI: 20479199

Redelman-Sidi G, Sepkowitz KA, Huang CK, Park S, Stiles J, Eagan J, Perlin DS, Pamer EG, Kamboj M (2010) 2009 H1N1 influenza infection in cancer patients and hematopoietic stem cell transplant recipients. J Infect 60: 257-263. PMI: 20138188

Puttikamonkul S, Willger SD, Grahl N, Perfect JR, Movahed N, Bothner B, Park S, Paderu P, Perlin DS, Cramer RA, Jr. (2010) Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus. Mol Microbiol. PMI: 20545865

Pfeiffer CD, Garcia-Effron G, Zaas AK, Perfect JR, Perlin DS, Alexander BD (2010) Breakthrough invasive candidiasis in patients on micafungin. J Clin Microbiol 48: 2373-2380. PMI: 20421445

Lin JS, Park S, Adamovicz JJ, Hill J, Bliska JB, Cote CK, Perlin DS, Amemiya K, Smiley ST (2010) TNFalpha and IFNgamma contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague. Vaccine 29: 357-362. PMI: 20840834

Koster F, Perlin DS, Park S, Brasel T, Gigliotti A, Barr E, Myers L, Layton RC, Sherwood R, Lyons CR (2010) Milestones in progression of primary pneumonic plague in cynomolgus macaques. Infect Immun 78: 2946-2955. PMI: 20385751

Garcia-Effron G, Chua DJ, Tomada JR, DiPersio J, Perlin DS, Ghannoum M, Bonilla H (2010) Novel FKS mutations associated with echinocandin resistance in Candida species. Antimicrob Agents Chemother 54: 2225-2227. PMI: 20145084

Gamarra S, Rocha EM, Zhang YQ, Park S, Rao R, Perlin DS (2010) Mechanism of the synergistic effect of amiodarone and fluconazole in Candida albicans. Antimicrob Agents Chemother 54: 1753-1761. PMI: 20194694

Do Y, Koh H, Park CG, Dudziak D, Seo P, Mehandru S, Choi JH, Cheong C, Park S, Perlin DS, Powell BS, Steinman RM (2010) Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague. Eur J Immunol 40: 2791-2796. PMI: 20812236

Boyer JL, Sofer-Podesta C, Ang J, Hackett NR, Chiuchiolo MJ, Senina S, Perlin D, Crystal RG (2010) Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid. Hum Gene Ther 21: 891-901. PMI: 20180652

Arendrup MC, Garcia-Effron G, Lass-Florl C, Lopez AG, Rodriguez-Tudela JL, Cuenca-Estrella M, Perlin DS (2010) Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media. Antimicrob Agents Chemother 54: 426-439. PMI: 19884370

Zhao Y, Park S, Kreiswirth BN, Ginocchio CC, Veyret R, Laayoun A, Troesch A, Perlin DS (2009) Rapid real-time nucleic Acid sequence-based amplification-molecular beacon platform to detect fungal and bacterial bloodstream infections. J Clin Microbiol 47: 2067-2078. PMI: 19403758

Sofer-Podesta C, Ang J, Hackett NR, Senina S, Perlin DS, Crystal RG, Boyer JL (2009) Adenovirus-mediated delivery of an anti-V antigen monoclonal antibody protects mice against a lethal Yersinia pestis challenge. Infect Immun 77: 1561-1568. PMI: 19124600

Perlin DS (2009) Antifungal drug resistance: do molecular methods provide a way forward? Curr Opin Infect Dis 22: 568-573. PMI: 19741524

Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, Pasqualotto AC, Laverdiere M, Arendrup MC, Perlin DS, Denning DW (2009) Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 15: 1068-1076. PMI: 19624922

Garcia-Effron G, Park S, Perlin DS (2009) Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother 53: 112-122. PMI: 18955538

Garcia-Effron G, Lee S, Park S, Cleary JD, Perlin DS (2009) Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother 53: 3690-3699. PMI: 19546367

Arendrup MC, Garcia-Effron G, Buzina W, Mortensen KL, Reiter N, Lundin C, Jensen HE, Lass-Florl C, Perlin DS, Bruun B (2009) Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment: laboratory characteristics and implication for susceptibility testing. Antimicrob Agents Chemother 53: 1185-1193. PMI: 19104024


Perlin, D.S. 2014. Echinocandin Resistance, Susceptibility Testing and Prophylaxis: Implications for Patient Management. Drugs. In press.

Zhao, Y. and Perlin, D.S. 2014.Use of novel tools to probe drug resistance in fungi. Springer. In press.

Drlica, K., J.-Y. Wang, M. Malik, T. Lu, C. Logan, S. Park, X. Li, D.S. Perlin, and X. Zhao. 2007. Antimicrobial Resistance and Implications for the 21st Century, Series: Emerging Infectious Diseases of the 21st Century. Fong, I.W.; Drlica, Karl (Eds.) Springer, NY.

Beauvais, A., Perlin, D.S., and Latgé, J.P. 2007. Role of (1-3) glucan in Aspergillus fumigatus and other human fungal pathogens. Fungi in the Environment Series: British Mycological Society Symposia (No. 25) Edited by Geoff Gadd, Sarah C. Watkinson and Paul Dyer, University of Oxford pp. 269-288.

Perlin D.S. 2008. Rapid Detection of Pathogens Bioterror: The Weaponization of Infectious Diseases. Larry I. Lutwick MD Suzanne M. Lutwick RN, BS, MPH Humana Press.

Perlin, D.S. 2007.Emerging Fungal Diseases. Emerging Infectious Diseases: Trends and Issues, 2nd ed. Editors: F. Lashley and J.D. Durham, Springer, NY.

Perlin, D.S. 2007. Multiplex detection of mutations. Methods in Molecular Biology. Editors: A. Marx and O. Seitz. The Humana Press Inc. NJ.

Perlin, D.S. 2007. Application of real-time PCR to the diagnosis of invasive fungal infections. Real-time PCR. Editors: K. Edwards, J. Logan and N. Saunders. Horizon Scientific Press. Norwich, UK.

Perlin, D.S. 2008. Antifungal Drug Resistance in Developing Countries. Editors: D.K. Byarugaba and A. Sosa. Springer, USA.

Perlin, D.S. and Mellado, E. 2008.Antifungal mechanisms of action and resistance. Aspergillus and Aspergillosis. Editors: W.J. Steinbach and J-P Latge, ASM Press.

Perlin, D.S. and W. Hope. 2009. Echinocandins. Aspergillosis: From diagnosis to prevention. Springer. The Netherlands

Perlin, D.S. 2008. Application of real-time PCR to the diagnosis of invasive fungal infections. Real-time PCR. Editors: K. Edwards, J. Logan and N. Saunders. Horizon Scientific Press. Norwich, UK.

Perlin, D.S. and W. Hope. 2009. Echinocandins. Aspergillosis: From diagnosis to prevention. Springer. The Netherlands.

Drlica, K. and Perlin, D.S. 2010 Antibiotic Resistance: Understanding and Responding to an Emerging Crisis. Published 2010 by FT Press.

Lewis, R. and Perlin, D.S. 2011. Fungal Drug Resistance and Pharmacologic Considerations of Dosing Newer Antifungal Therapies. "Management of Infections in Cancer Patients" Current Clinical Oncology Safdar, Amar (Ed.) 1st Edition.


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