2023
Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist. Nichols DP, Morgan SJ, Skalland M, Vo AT, Van Dalfsen JM, Singh SBP, Ni W, Hoffman LR, McGeer K, Heltshe SL, Clancy JP, Rowe SM, Jorth P, Singh PK. J Clin Invest. 2023 May 15;133(10):e167957. https://doi: 10.1172/JCI167957
2022
Genome Capture Sequencing Selectively Enriches Bacterial DNA and Enables Genome-Wide Measurement of Intrastrain Genetic Diversity in Human Infections. Hayden HS, Joshi S, Radey MC, Vo AT, Forsberg C, Morgan SJ, Waalkes A, Holmes EA, Klee SM, Emond MJ, Singh PK, Salipante SJ. mBio 2022 September 19 https://doi.org/10.1128/mbio.01424-22
The Depletion Mechanism Actuates Bacterial Aggregation by Exopolysaccharides and Determines Species Distribution & Composition in Bacterial Aggregates. Secor PR, Michaels LA, Bublitz DC, Jennings LK, Singh PK. Front. Cell. Infect. Microbiol 2022 June 16 https://doi.org/10.3389/fcimb.2022.869736
2021
A population-level strain genotyping method to study pathogen strain dynamics in human infections. Morgan SJ, Durfey SL, Ravishankar S, Jorth P, Ni W, Skerrett DT, Aitken ML, McKone EF, Salipante SJ, Radey MC, Singh PK. JCI Insight. 2021 Dec 22. 2021;6(24):e152472. https://doi.org/10.1172/jci.insight.152472.
Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections. Durfey SL, Pipavath S, Li A, Vo AT, Ratjen A, Carter S, Morgan SJ , Radey MC, Grogan B, Salipante SJ, Welsh MJ, Stoltz DA, Goss CH, McKone EF, Singh PK. mBio 2021 December 14 https://doi.org/10.1128/mbio.03148-21
Testing the effects of combining azithromycin with inhaled tobramycin for P. aeruginosa in cystic fibrosis: a randomised, controlled clinical trial. Nichols DP, Singh PK, Baines A, Caverly LJ, Chmiel JF, Gibson RL, Lascano J, Morgan SJ, Retsch-Bogart G, Saiman L, Sadeghi H, Billings JL, Heltshe SL, Kirby S, Kong A, Nick JA, Nicole Mayer-Hamblett NM, TEACH Study Group. Thorax P 2021 October 27. doi: 10.1136/thoraxjnl-2021-217782
Ivacaftor modifies cystic fibrosis neutrophil phenotype in subjects with R117H residual function CFTR mutations. Hardisty GR, Law SM, Carter S, Grogan B, Singh PK, McKone EF, Gray RD. Eur Respir J. 2021 Jan 21;57(1):2002161.
Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation. Keating CL, Zuckerman JB, Singh PK, McKevitt M, Gurtovaya O, Bresnik M, Marshall BC, Saiman L. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02327-20.
Cystic Fibrosis Lung Function Decline after Within-Host Evolution Increases Virulence of Infecting Pseudomonas aeruginosa. Jorth P, Durfey S, Rezayat A, Garudathri J, Ratjen A, Staudinger BJ, Radey MC, Genatossio A, McNamara S, Cook DA, Aitken ML, Gibson RL, Yahr TL, Singh PK. Am J Respir Crit Care Med. 2021 Mar 1;203(5):637-640.
PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy. Nichols DP, Donaldson SH, Frederick CA, Freedman SD, Gelfond D, Hoffman LR, Kelly A, Narkewicz MR, Pittman JE, Ratjen F, Sagel SD, Rosenfeld M, Schwarzenberg SJ, Singh PK, Solomon GM, Stalvey MS, Kirby S, VanDalfsen JM, Clancy JP, Rowe SM. J Cyst Fibros. 2021 Mar;20(2):205-212.
Inflammatory cytokines TNF-α and IL-17 enhance the efficacy of cystic fibrosis transmembrane conductance regulator modulators. Rehman T, Karp PH, Tan P, Goodell BJ, Pezzulo AA, Thurman AL, Thornell IM, Durfey SL, Duffey ME, Stoltz DA, McKone EF, Singh PK, Welsh MJ. J Clin Invest. 2021 Aug 16;131(16):e150398.
2020
Bacterial fitness in chronic wounds appears to be mediated by the capacity for high-density growth, not virulence or biofilm functions. Morgan SJ, Lippman SI, Bautista GE, Harrison JJ, Harding CL, Gallagher LA, Cheng A, Siehnel R, Ravishankar S, Usui ML, Olerud JE, Fleckman P, Wolcott RD, Manoil C, Singh PK. PLoS Pathog. 2019 Mar 20;15(3):e1007511.
Cell free DNA from respiratory pathogens is detectable in the blood plasma of Cystic Fibrosis patients. Barrett SLR, Holmes EA, Long DR, Shean RC, Bautista GE, Ravishankar S, Peddu V, Cookson BT, Singh PK, Greninger AL, Salipante SJ. Sci Rep. 2020 Apr 23;10(1):6903.
2019
Direct Lung Sampling Indicates That Established Pathogens Dominate Early Infections in Children with Cystic Fibrosis. Jorth P, Ehsan Z, Rezayat A, Caldwell E, Pope C, Brewington JJ, Goss CH, Benscoter D, Clancy JP, Singh PK. Cell Rep. 2019 Apr 23;27(4):1190-1204.e3.
In Vivo Proteome of Pseudomonas aeruginosain Airways of Cystic Fibrosis Patients. Wu X, Siehnel RJ, Garudathri J, Staudinger BJ, Hisert KB, Ozer EA, Hauser AR, Eng JK, Manoil C, Singh PK, Bruce JE. J Proteome Res. 2019 Jun 7;18(6):2601-2612.
2018
Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis. Gray RD, Hardisty G, Regan KH, Smith M, Robb CT, Duffin R, Mackellar A, Felton JM, Paemka L, McCullagh BN, Lucas CD, Dorward DA, McKone EF, Cooke G, Donnelly SC, Singh PK, Stoltz DA, Haslett C, McCray PB, Whyte MKB, Rossi AG, Davidson DJ. Thorax. 2018 Feb;73(2):134-144.
Determinants of Extreme β-Lactam Tolerance in the Burkholderia pseudomallei Complex. Held K, Gasper J, Morgan S, Siehnel R, Singh PK, Manoil C. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e00068-18.
Ivacaftor-induced sweat chloride reductions correlate with increases in airway surface liquid pH in cystic fibrosis. Abou Alaiwa MH, Launspach JL, Grogan B, Carter S, Zabner J, Stoltz DA, Singh PK, McKone EF, Welsh MJ. JCI Insight. 2018 Aug 9;3(15):e121468.
Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections. Goss CH, Kaneko Y, Khuu L, Anderson GD, Ravishankar S, Aitken ML, Lechtzin N, Zhou G, Czyz DM, McLean K, Olakanmi O, Shuman HA, Teresi M, Wilhelm E, Caldwell E, Salipante SJ, Hornick DB, Siehnel RJ, Becker L, Britigan BE, Singh PK. Sci Transl Med. 2018 Sep 26;10(460):eaat7520.
2017
Evolved Aztreonam Resistance Is Multifactorial and Can Produce Hypervirulence in Pseudomonas aeruginosa. Jorth P, McLean K, Ratjen A, Secor PR, Bautista GE, Ravishankar S, Rezayat A, Garudathri J, Harrison JJ, Harwood RA, Penewit K, Waalkes A, Singh PK, Salipante SJ. mBio. 2017 Oct 31;8(5):e00517-17.
Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections. Hisert KB, Heltshe SL, Pope C, Jorth P, Wu X, Edwards RM, Radey M, Accurso FJ, Wolter DJ, Cooke G, Adam RJ, Carter S, Grogan B, Launspach JL, Donnelly SC, Gallagher CG, Bruce JE, Stoltz DA, Welsh MJ, Hoffman LR, McKone EF, Singh PK. Am J Respir Crit Care Med. 2017 Jun 15;195(12):1617-1628.
2016
In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in antibiotic resistant bacteria. Wu X; Chavez J, Schweppe DK, Zheng C, Weisbrod C, Eng J, Murali A, Lee S, Ramage E, Gallagher L, Kulasekara H, Edrozo M, Kamischke C, Brittnacher M, Miller SI, Singh PK, Manoil C, Bruce JE. Nat Commun. 2016 Nov 11;7:13414
Filamentous bacteriophage produced by Pseudomonas aeruginosa alters the inflammatory response and promotes non-invasive infection in vivo. Secor PR, Michaels LA, Smigiel KS, Rohani MG, Jennings LK Hisert KB, Arrigoni A, Braun KR, Birkland TP; Lai Y, Hallstrant TR, Bollyky PL, Singh PK, Parks WC. Infect Immun. 2016 Dec 29;85(1).
Ivacaftor-induced proteomic changes suggest monocyte defects may contribute to the pathogenesis of cystic fibrosis. Hisert KB, Schoenfelt KQ, Cooke, G, Grogan B, Launspach JL, Gallagher CG, Donnelly SC, McKone EF, Welsh MJ, Singh PK, Becker L. Am J Respir Cell Mol Bio, Am J Respir Cell Mol Biol. 2016 Apr;54(4):594-7. doi: 10.1165/rcmb.2015-0322LE.
Acute Administration of Ivacaftor to People with Cystic Fibrosis and a G551D-CFTR Mutation Reveals Smooth Muscle Abnormalities. Adam RJ, Hisert KB, Jonathan D. Dodd JD, Grogan B, Barnes JK, Gallagher CG, Sieren JP, Gross TJ, Fischer AJ, Cavanaugh JE, Hoffman EA, Singh PK, Welsh MJ, McKone EF, Stoltz DA. JCI Insight. 2016 Apr 7;1(4):e86183.
2015
Host-Microbe Protein Interactions during Bacterial Infection. Schweppe DK, Harding C, Chavez JD, Wu X, Ramage E, Singh PK, Manoil C, Bruce JE. Chem Biol. 2015 Nov 19;22(11):1521-30. doi: 10.1016/j.chembiol.2015.09.015. Epub 2015 Nov 5. PMID: 26548613
Probing the protein interaction network of Pseudomonas aeruginosa cells by chemical cross-linking mass spectrometry. Navare AT, Chavez JD ,Zheng C, Weisbrod CR, Eng JK, Siehnel R, Singh PK, Manoil C, Bruce JE, Structure 2015 Apr 7;23(4):762-73. doi: 10.1016/j.str.2015.01.022. Epub 2015 Mar 19. PMID: 25800553.
General and condition-specific essential genes of Pseudomonas aeruginosa. Lee S, Gallagher L, Thongdee B, Staudinger B, Lippman S, Singh PK, Manoil C Proc Natl Acad Sci USA. 2015 Apr 21;112(16):5189-94. doi: 10.1073/pnas.1422186112. Epub 2015 Apr 6.
Dynamic Proteome Response of Pseudomonas aeruginosa to Tobramycin Antibiotic Treatment. Wu X, Held K, Zheng C, Staudinger BJ, Chavez JD, Weisbrod CR, Eng JK, Singh PK, Manoil C, Bruce JE. Mol Cell Proteomics. 2015 Aug;14(8):2126-37. doi: 10.1074/mcp.M115.050161. Epub 2015 May 27.
Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus. Abdalla MY, Switzer BL, Goss CH, Aitken ML, Singh PK, Britigan BE. Antimicrob Agents Chemother. 2015 Aug;59(8):4826-34. doi: 10.1128/AAC.00331-15. Epub 2015 Jun 1.
Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange. Hmelo L, Borlee BR, Almblad H, Randall TE, Love ME, Yang JJ, Irie Y, Tseng BS, Storek KM, Siehnel RJ, P. Howell LS, Singh PK, Tolker-Nielsen T, Parsek MR, and Harrison JJ. Nature Protocols, 2015 Nov;10(11):1820-41
Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs. Staudinger BJ, Wu X, Jorth P, Hisert K, Garudathri J, Hayden H, Harding C, Radey MC, Barrington W, Goddard AF, Angermeyer A, Brittnacher MJ, Shendure J, Kitzmam J, Fligner C, Aitken ML, Manoil C, Bruce JE, Yahr TL, and Singh PK, Cell Host and Microbe, 2015 Sep 9;18(3):307-19. Cover article
Host-Microbe Protein Interactions during Bacterial Infection. Schweppe DK, Singh PK, Manoil C, Bruce JE. Chemistry & Biology 2015 Nov 19;22(11):1521-30.
Filamentous Bacteriophage Promote Biofilm Assembly and Function. Secor PR, Sweere JM, Michaels LA, Malkovskiy AV, Lazzareschi D, Katznelson E, Rajadas J, Birnbaum ME, Arrigoni A, Braun KR, Evanko SP, Stevens DA, Kaminsky W, Singh PK, Parks WC, Bollyky PL. Cell Host Microbe. 2015 Nov 11;18(5):549-59.
2014
Rapid Evolution of Culture-Resistant Bacteria During Adaptation to Biofilm Growth. Penterman J, Nguyen D, Staudinger B, Anderson E, Greenberg EP, Lam JS, and Singh, PK. Cell Reports. 2014 Jan 30;6(2):293-300. doi: 10.1016/j.celrep.2013.12.019. Epub 2014 Jan 9. PMID: 24412364
Conditions Associated with the CF Defect Promote Chronic P. aeruginosa Infection. Staudinger B, Muller JF, Halldórsson S, Boles BR, Angermeyer A, Nguyen D, Rosen H, Baldursson O, Gottfreðsson M, Guðmundsson GH, and Singh PK. Am J Respir Crit Care Med. 2014 Apr 1;189(7):812-24. doi: 10.1164/rccm.201312-2142OC. PMID: 24467627
Biological cost of pyocin production during the SOS response in Pseudomonas aeruginosa. Penterman J, Singh PK, Walker GC. J Bacteriol. 2014 Jul 14. pii: JB.01889-14.
Metabolic dysfunction drives a unique pro-inflammatory phenotype in human adipose tissue macrophages. Kratz M, Hisert K, Hagman E, Peris E, Schoenfelt K, Coats B, Kuzma J, Larson I, Billing P, Landerholm RW, Crouthamel M, Singh PK, and Becker L. Cell Metabolism. 2014 Oct 7;20(4):614-25. (Cover article).
2013
The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin. Tseng BS, Zhang W, Harrison JJ, Quach TP, Song JL, Penterman J, Singh PK, Chopp DL, Packman AI, Parsek MR. Environ Microbiol. 2013 May 13.
2012 and earlier
Future Directions in Early Cystic Fibrosis Lung Disease Research. Ramsey BW, Schlegel SB, Accurso FJ, Boucher RC, Cutting GR, Engelhardt JF, Guggino WB, Karp CL, Knowles MR, Kolls JK, LiPuma JJ, Lynch S, McCray PB, Rubenstein RC, Singh PK, Sorscher E, Welsh MJ. Am J Respir Crit Care Med. 2012 Apr 15;185(8):887-92.
Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper airway specimens can misrepresent infecting populations. Goddard, A F, Staudinger, B J, Dowd SE, Datar A, Wolcott RD, Aitken ML, Fligner CL, and Singh, PK; Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13769-74.
Active starvation responses mediate antibiotic tolerance in biofilms and nutrient limited bacteria. Nguyen D, Lepine F, Datar A, Bauerle E, Olakanmi O, Beer K, McKay G, Siehnel R, Schafhauser J, Britigan B and Singh, PK. Science Nov 18; 334(6058):982-6.
Azithromycin maintains airway epithelial integrity during Pseudomonas aeruginosa infections. Halldorsson S, Gudjonsson T, Gottfredsson M, Singh PK, Baldursson O: Am. J. Resp. Cell. Mol. Bio. 2010 Jan;42(1):62-8. Cover article
PLUNC is a Novel Surfactant Protein Secreted by Conducting Airway Epithelia. Gakhar L, Bartlett JA, Penterman J, Mizrachi D, Singh PK, Mallampalli RK, Ramaswamy S, McCray PB. PLOS ONE, 2010 Feb 9;5(2):e9098
A unique regulator controls the activation threshold of quorum-regulated genes in Pseudomonas aeruginosa. Siehnel R, Traxler B, Parsek, M, Schaefer A, Singh PK. Proc Natl Acad Sci. 2010 Apr 27;107(17):7916-21.
Delayed Wound Healing in Diabetic (db/db) Mouse with Pseudomonas aeruginosa Biofilm Infections, A Model for the Study of Chronic Wounds. Wound Repair Regen. Zhao G, Hochwalt P, Usui M, Underwood R, Singh PK, James G, Stewart P, Olerud J, Fleckman P: 2010 Sep-Oct;18(5):467-77.
Targeting bacterial stress responses to enhance antibiotic action. Lee S, Hinz A, Bauerle E, Angermyer A, Juhaszova, K, Kaneko Y, Singh PK, Manoil C: Proc Natl Acad Sci 2009 Aug 25;106(34):14570-5.
Endogenous Oxidative Stress Produces Diversity and Adaptability in Biofilm Communities. Boles BR and Singh PK: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12503-8.
The transition metal gallium disrupts iron metabolism in P. aeruginosa and has anti-microbial and anti-biofilm action. Kaneko Y, Thoendel M, Olakanmi O, Britigan BE, Singh PK: J. Clin. Invest. Apr;117(4):877-88, 2007.
Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production. Soong, G, Muir A, Gomez M, Reddy B, Planet P, Singh PK, Kaneko Y, Wolfgang MC, Prince A: J. Clin. Invest. Aug;116(8):2297-2305, 2006.
Mucin-Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance. Landry RM, An D, Hupp JT, Singh PK, Parsek MR:. Mol. Microbiol., Jan;59(1):142-51, 2006.
Evolving stealth: genetic adaptation of Pseudomonas aeruginosa during cystic fibrosis infections. Nguyen D, Singh PK., Proc Natl Acad Sci U S A. 2006 May 30;103(22):8305-6.
Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial cells. Garcia-Medina R, Dunne WM, Singh PK, Brody SL: Infect. Immun. Dec;73(12):8298-305, 2005.
Genetic variation in biofilms and the insurance effects of diversity. Boles BR, Thoendel M, Singh PK: Microbiology, 151(Pt 9):2816-8, 2005.
Rhamnolipids Mediate Detachment of Pseudomonas aeruginosa from Biofilms. Boles BR, Thoendel M, Singh PK: Mol. Micrbiol., 57(5):1210-23, 2005. Cover article
Cystic Fibrosis Sputum Supports Growth and Cues Key Aspects of Pseudomonas aeruginosa. Physiology. Palmer KL, Mashburn LM, Singh PK, Whiteley M: J Bacteriol, 187(15):5267-77, 2005.
Iron Sequestration by Human Lactoferrin Stimulates P. aeruginosa Surface Motility and Blocks Biofilm Formation. Singh PK: BioMetals 17(3):267-70, 2004. Boles BR, Thoendel M, Singh PK: Self-Generated Diversity Produces “Insurance Effects” in Biofilm Communities. Proc. Natl. Acad. Sci. USA, 101(47):16630-5, 2004.
Bacterial Biofilms: An Emerging Link to Disease Pathogenesis. Parsek MR, Singh PK:, Annu. Rev. Microbiol., 57:677-701, 2003.
A Component of Innate Immunity Prevents Bacterial Biofilm Development. Singh PK, Parsek MR, Greenberg EP, Welsh MJ: Nature, 417:552-5, 2002.
ExsD is a Negative Regulator of the Pseudomonas aeruginosa Type III Section Regulon. McCaw ML, Lykken L, Singh PK, and Yahr, TL: Mol. Microbiol, 46:1123-1133, 2002.
Antimicrobial Peptides and Proteins in the Innate Defense of the Airway Surface. Travis SM, Singh PK, Welsh MJ; Curr. Opin. Immunol., 13(1):89-95, 2001.
Lactoferrin, An Antimicrobial Factor of Human Airways, Prevents Biofilm Formation by P. aeruginosa. Singh PK, Parsek MR, Welsh MJ, Greenberg EP: Pediatr. Pulmonol., 32:282, 2001.
Synergistic and Additive Killing by Antimicrobial Factors Found in Human Airway Surface Liquid. Singh PK, Tack BF, McCray PB, Welsh MJ: Am. J. Physiol., 279(5):L799-L805, 2000.
Quorum-Sensing Signals Indicate that Cystic Fibrosis Lungs are Infected with Bacterial Biofilms. Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP: Nature, 407(6805):762-764, 2000.
Activity of Abundant Antimicrobials of the Human Airway. Travis SM, Conway B-AD, Zabner J, Smith JJ, Anderson NN, Singh PK, Greenberg EP, Welsh MJ: Am. J. Respir. Cell Mol. Biol., 20(5):872-879, 1999.
Production of ß-Defensins by Human Airway Epithelia. Singh PK, Jia H-P, Wiles K, Hesselberth J, Liu L, Conway B-A D, Greenberg EP, Valore EV, Welsh MJ, Ganz T, Tack BF, McCray PB Jr: Proc. Natl. Acad. Sci. USA, 95(25):14961-14966, 1998.