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.

Key words： Pseudomonas aeruginosa; cystic fibrosis; evolution; adaptive radiation; antibiotic resistance; quorum sensing

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

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