Universal soldier: Pseudomonas aeruginosa – an opportunistic generalist

Abstract

The opportunistic pathogen Pseudomonas aeruginosa commonly causes chronic and ultimately deadly lung infections in individuals with the genetic disease cystic fibrosis (CF). P. aeruginosa is metabolically diverse; it displays a remarkable ability to adapt to and successfully occupy almost any niche, including the ecologically complex CF lung. These P. aeruginosa lung infections are a fascinating example of microbial evolution within a “natural” ecosystem. Initially, P. aeruginosa shares the lung niche with a plethora of other microorganisms and is vulnerable to antibiotic challenges. Over time, adaptive evolution leads to certain commonly-observed phenotypic changes within the P. aeruginosa population, some of which render it resistant to antibiotics and apparently help it to out-compete the other species that co-habit the airways. Improving genomics techniques continue to elucidate the evolutionary mechanisms of P. aeruginosa within the CF lung and will hopefully identify new vulnerabilities in this robust and versatile pathogen.

Keywords

Pseudomonas aeruginosa / cystic fibrosis / evolution / adaptive radiation / antibiotic resistance / quorum sensing

References

[1] Bjarnsholt T, Jensen P Ø, Jakobsen T H, Phipps R, Nielsen A K, Rybtke M T, Tolker-Nielsen T, Givskov M, Høiby N, Ciofu O (2010). Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS ONE, 5(4): e10115

[2] Brockhurst M A, Colegrave N, Hodgson D J, Buckling A (2007). Niche occupation limits adaptive radiation in experimental microcosms. PLoS ONE, 2(2): e193

[3] Buckling A, Wills M A, Colegrave N (2003). Adaptation limits diversification of experimental bacterial populations. Science, 302(5653): 2107–2109

[4] Chugani S, Kim B S, Phattarasukol S, Brittnacher M J, Choi S H, Harwood C S, Greenberg E P (2012). Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon. Proc Natl Acad Sci USA, 109(41): E2823–E2831

[5] Chung J C S, Becq J, Fraser L, Schulz-Trieglaff O, Bond N J, Foweraker J, Bruce K D, Smith G P, Welch M (2012). Genomic variation among contemporary Pseudomonas aeruginosa isolates from chronically infected cystic fibrosis patients. J Bacteriol, 194(18): 4857–4866

[6] Collier D N, Anderson L, McKnight S L, Noah T L, Knowles M, Boucher R, Schwab U, Gilligan P, Pesci E C (2002). A bacterial cell to cell signal in the lungs of cystic fibrosis patients. FEMS Microbiol Lett, 215(1): 41–46

[7] Cox M J, Allgaier M, Taylor B, Baek M S, Huang Y J, Daly R A, Karaoz U, Andersen G L, Brown R, Fujimura K E, Wu B, Tran D, Koff J, Kleinhenz M E, Nielson D, Brodie E L, Lynch S V (2010). Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS ONE, 5(6): e11044

[8] Cramer N, Klockgether J, Wrasman K, Schmidt M, Davenport C F, Tümmler B (2011). Microevolution of the major common Pseudomonas aeruginosa clones C and PA14 in cystic fibrosis lungs. Environ Microbiol, 13(7): 1690–1704

[9] Daniels T W V, Rogers G B, Stressmann F A, van der Gast C J, Bruce K D, Jones G R, Connett G J, Legg J P, Carroll M P (2013). Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis. J Cyst Fibros, 12(1): 22–28

[10] Diggle S P, Griffin A S, Campbell G S, West S A (2007). Cooperation and conflict in quorum-sensing bacterial populations. Nature, 450(7168): 411–414

[11] Foweraker J (2009). Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br Med Bull, 89(1): 93–110

[12] Govan J R, Deretic V (1996). Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev, 60: 539–574

[13] Guss A M, Roeselers G, Newton I L G, Young C R, Klepac-Ceraj V, Lory S, Cavanaugh C M (2011). Phylogenetic and metabolic diversity of bacteria associated with cystic fibrosis. ISME J, 5(1): 20–29

[14] Hardin G (1960). The competitive exclusion principle. Science, 131(3409): 1292–1297

[15] Häussler S, Tümmler B, Weissbrodt H, Rohde M, Steinmetz I (1999). Small-colony variants of Pseudomonas aeruginosa in cystic fibrosis. Clin Infect Dis, 29(3): 621–625

[16] Häussler S, Ziegler I, Löttel A, von Götz F, Rohde M, Wehmhöhner D, Saravanamuthu S, Tümmler B, Steinmetz I (2003). Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. J Med Microbiol, 52(4): 295–301

[17] Hobbs E C, Fontaine F, Yin X, Storz G (2011). An expanding universe of small proteins. Curr Opin Microbiol, 14(2): 167–173

[18] Jacobs M A, Alwood A, Thaipisuttikul I, Spencer D, Haugen E, Ernst S, Will O, Kaul R, Raymond C, Levy R, Liu C R, Guenthner D, Bovee D, Olson M V, Manoil C (2003). Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci USA, 100(24): 14339–14344

[19] James C E, Fothergill J L, Kalwij H, Hall A J, Cottell J, Brockhurst M A, Winstanley C (2012). Differential infection properties of three inducible prophages from an epidemic strain of Pseudomonas aeruginosa. BMC Microbiol, 12(1): 216

[20] Klockgether J, Miethke N, Kubesch P, Bohn Y S, Brockhausen I, Cramer N, Eberl L, Greipel J, Herrmann C, Herrmann S, Horatzek S, Lingner M, Luciano L, Salunkhe P, Schomburg D, Wehsling M, Wiehlmann L, Davenport C F, Tümmler B (2013). Intraclonal diversity of the Pseudomonas aeruginosa cystic fibrosis airway isolates TBCF10839 and TBCF121838: distinct signatures of transcriptome, proteome, metabolome, adherence and pathogenicity despite an almost identical genome sequence. Environ Microbiol, 15(1): 191–210

[21] Kumar A, Schweizer H P (2005). Bacterial resistance to antibiotics: active efflux and reduced uptake. Adv Drug Deliv Rev, 57(10): 1486–1513

[22] Lorè N I, Cigana C, De Fino I, Riva C, Juhas M, Schwager S, Eberl L, Bragonzi A (2012). Cystic fibrosis-niche adaptation of Pseudomonas aeruginosa reduces virulence in multiple infection hosts. PLoS ONE, 7(4): e35648

[23] MacLean R C (2005). Adaptive radiation in microbial microcosms. J Evol Biol, 18(6): 1376–1386

[24] MacLean R C, Bell G, Rainey P B (2004). The evolution of a pleiotropic fitness tradeoff in Pseudomonas fluorescens. Proc Natl Acad Sci USA, 101(21): 8072–8077

[25] Mathee K, Narasimhan G, Valdes C, Qiu X, Matewish J M, Koehrsen M, Rokas A, Yandava C N, Engels R, Zeng E, Olavarietta R, Doud M, Smith R S, Montgomery P, White J R, Godfrey P A, Kodira C, Birren B, Galagan J E, Lory S (2008). Dynamics of Pseudomonas aeruginosa genome evolution. Proc Natl Acad Sci USA, 105(8): 3100–3105

[26] Mowat E, Paterson S, Fothergill J L, Wright E A, Ledson M J, Walshaw M J, Brockhurst M A, Winstanley C (2011). Pseudomonas aeruginosa population diversity and turnover in cystic fibrosis chronic infections. Am J Respir Crit Care Med, 183(12): 1674–1679

[27] Oliver A, Cantón R, Campo P, Baquero F, Blázquez J (2000). High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science, 288(5469): 1251–1253

[28] Pritt B, O’Brien L, Winn W (2007). Mucoid Pseudomonas in cystic fibrosis. Am J Clin Pathol, 128(1): 32–34

[29] Rainey P B, Travisano M (1998). Adaptive radiation in a heterogeneous environment. Nature, 394(6688): 69–72

[30] Rau M H, Marvig L R, Ehrlich G D, Molin S, Jelsbak L (2012). Deletion and acquisition of genomic content during early stage adaptation of Pseudomonas aeruginosa to a human host environment. Environ Microbiol, 14(8): 2200–2211

[31] Rogers G B, Carroll M P, Serisier D J, Hockey P M, Jones G, Bruce K D (2004). Characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16s ribosomal DNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol, 42(11): 5176–5183

[32] Rogers G B, Hart C A, Mason J R, Hughes M, Walshaw M J, Bruce K D (2003). Bacterial diversity in cases of lung infection in cystic fibrosis patients: 16S ribosomal DNA (rDNA) length heterogeneity PCR and 16S rDNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol, 41(8): 3548–3558

[33] Roy P H, Tetu S G, Larouche A, Elbourne L, Tremblay S, Ren Q, Dodson R, Harkins D, Shay R, Watkins K, Mahamoud Y, Paulsen I T (2010). Complete genome sequence of the multiresistant taxonomic outlier Pseudomonas aeruginosa PA7. PLoS ONE, 5(1): e8842

[34] Singh P K, Schaefer A L, Parsek M R, Moninger T O, Welsh M J, Greenberg E P (2000). Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature, 407(6805): 762–764

[35] Smith E E, Buckley D G, Wu Z, Saenphimmachak C, Hoffman L R, D’Argenio D A, Miller S I, Ramsey B W, Speert D P, Moskowitz S M, Burns J L, Kaul R, Olson M V, Affiliations A (2006). Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci USA, 103(22): 8487–8492

[36] Spiers A J, Buckling A, Rainey P B (2000). The causes of Pseudomonas diversity. Microbiology (Reading, Engl.), 146 (Pt 10): 2345–2350.

[37] Starkey M, Hickman J H, Ma L, Zhang N, De Long S, Hinz A, Palacios S, Manoil C, Kirisits M J, Starner T D, Wozniak D J, Harwood C S, Parsek M R (2009). Pseudomonas aeruginosa rugose small-colony variants have adaptations that likely promote persistence in the cystic fibrosis lung. J Bacteriol, 191(11): 3492–3503

[38] Stickland H G, Davenport P W, Lilley K S, Griffin J L, Welch M (2010). Mutation of nfxB causes global changes in the physiology and metabolism of Pseudomonas aeruginosa. J Proteome Res, 9(6): 2957–2967

[39] Stover C K, Pham X Q, Erwin A L, Mizoguchi S D, Warrener P, Hickey M J, Brinkman F S, Hufnagle W O, Kowalik D J, Lagrou M, Garber R L, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody L L, Coulter S N, Folger K R, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong G K, Wu Z, Paulsen I T, Reizer J, Saier M H, Hancock R E, Lory S, Olson M V (2000). Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature, 406(6799): 959–964

[40] Stressmann F A, Rogers G B, van der Gast C J, Marsh P, Vermeer L S, Carroll M P, Hoffman L, Daniels T W V, Patel N, Forbes B, Bruce K D (2012). Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience. Thorax, 67(10): 867–873

[41] Tunney M M, Field T R, Moriarty T F, Patrick S, Doering G, Muhlebach M S, Wolfgang M C, Boucher R, Gilpin D F, McDowell A, Elborn J S (2008). Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med, 177(9): 995–1001

[42] van der Gast C J, Walker A W, Stressmann F A, Rogers G B, Scott P, Daniels T W, Carroll M P, Parkhill J, Bruce K D (2011). Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities. ISME J, 5(5): 780–791

[43] Williams P, Camara M (2009). Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol, 12(2): 182–191

[44] Winstanley C, Langille M G, Fothergill J L, Kukavica-Ibrulj I, Paradis-Bleau C, Sanschagrin F, Thomson N R, Winsor G L, Quail M A, Lennard N, Bignell A, Clarke L, Seeger K, Saunders D, Harris D, Parkhill J, Hancock R E, Brinkman F S, Levesque R C (2009). Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. Genome Res, 19(1): 12–23

[45] Workentine M L, Sibley C D, Glezerson B, Purighalla S, Norgaard-Gron J C, Parkins M D, Rabin H R, Surette M G (2013). Phenotypic heterogeneity of Pseudomonas aeruginosa. Populations in a Cystic Fibrosis Patient. PLoS ONE, 8(4): e60225

[46] Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A, Meyer K C, Birrer P, Bellon G, Berger J, Weiss T, Botzenhart K, Yankaskas J R, Randell S, Boucher R C, Döring G (2002). Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest, 109: 317–325

[47] Wurtzel O, Yoder-Himes D R, Han K, Dandekar A A, Edelheit S, Greenberg E P, Sorek R, Lory S (2012). The Single- Nucleotide Resolution Transcriptome of Pseudomonas aeruginosa Grown in Body Temperature. PLoS Pathog, 8(9): e1002945

[48] Yang L, Jelsbak L, Marvig R L, Damkiær S, Workman C T, Rau M H, Hansen S K, Folkesson A, Johansen H K, Ciofu O, Hoiby N, Sommer M O A, Molin S (2011). Evolutionary dynamics of bacteria in a human host environment. Proc Natl Acad Sci USA, 108(18): 7481–7486

[49] Zhao J, Schloss P D, Kalikin L M, Carmody L A, Foster B K, Petrosino J F, Cavalcoli J D, VanDevanter D R, Murray S, Li J Z, Young V B, LiPuma J (2012). Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci, 109: 5809–5814

Acknowledgements

This review is not intended to be exhaustive and we apologize to colleagues whose work is not cited for space reasons. Work in the laboratory of MW is funded by the BBSRC and Isaac Newton Trust.

Compliance with ethics guidelines

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg