Host Adaptation Predisposes Pseudomonas Aeruginosa to Type VI Secretion System-Mediated Predation by the Burkholderia Cepacia Complex

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2020 Aug 7

PMID 32755549

Citations 24

Authors

Andrew I Perault

Courtney E Chandler

David A Rasko

Robert K Ernst

Matthew C Wolfgang

Peggy A Cotter

Affiliations

Soon will be listed here.

Abstract

Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species are opportunistic lung pathogens of cystic fibrosis (CF) patients. While P. aeruginosa can initiate long-term infections in younger CF patients, Bcc infections only arise in teenagers and adults. Both P. aeruginosa and Bcc use type VI secretion systems (T6SSs) to mediate interbacterial competition. Here, we show P. aeruginosa isolates from teenage and adult CF patients, but not those from young CF patients, are outcompeted by the epidemic Bcc isolate Burkholderia cenocepacia strain AU1054 in a T6SS-dependent manner. The genomes of susceptible P. aeruginosa isolates harbor T6SS-abrogating mutations, the repair of which, in some cases, rendered the isolates resistant. Moreover, seven of eight Bcc strains outcompeted P. aeruginosa strains isolated from the same patients. Our findings suggest certain mutations that arise as P. aeruginosa adapts to the CF lung abrogate T6SS activity, making P. aeruginosa and its human host susceptible to potentially fatal Bcc superinfection.

Citing Articles

Decoding resistance in the age of T6SS warfare.

Shikuma N Proc Natl Acad Sci U S A. 2025; 122(7):e2500342122.

PMID: 39928881 PMC: 11848427. DOI: 10.1073/pnas.2500342122.

Multiplicity of type 6 secretion system toxins limits the evolution of resistance.

Smith W, Armstrong-Bond E, Coyte K, Knight C, Basler M, Brockhurst M Proc Natl Acad Sci U S A. 2025; 122(2):e2416700122.

PMID: 39786933 PMC: 11745330. DOI: 10.1073/pnas.2416700122.

A type VI secretion system in species and triggers distinct macrophage death pathways independent of the pyrin inflammasome.

Loeven N, Dabi C, Pennington J, Reuven A, McGee A, Mwaura B Infect Immun. 2024; 92(12):e0031624.

PMID: 39480100 PMC: 11629634. DOI: 10.1128/iai.00316-24.

Phage-mediated resolution of genetic conflict alters the evolutionary trajectory of lysogens.

Suttenfield L, Rapti Z, Chandrashekhar J, Steinlein A, Vera J, Kim T mSystems. 2024; 9(9):e0080124.

PMID: 39166874 PMC: 11406979. DOI: 10.1128/msystems.00801-24.

utilizes a unique type VI secretion system to promote its survival in niches with prey bacteria.

Sun Y, Wang L, Zhang M, Jie J, Guan Q, Fu J mBio. 2024; 15(7):e0146824.

PMID: 38916378 PMC: 11253628. DOI: 10.1128/mbio.01468-24.

References

Filkins L, OToole G . Cystic Fibrosis Lung Infections: Polymicrobial, Complex, and Hard to Treat. PLoS Pathog. 2016; 11(12):e1005258. PMC: 4700991. DOI: 10.1371/journal.ppat.1005258. View

Brencic A, Lory S . Determination of the regulon and identification of novel mRNA targets of Pseudomonas aeruginosa RsmA. Mol Microbiol. 2009; 72(3):612-32. PMC: 5567987. DOI: 10.1111/j.1365-2958.2009.06670.x. View

Zhao J, Schloss P, Kalikin L, Carmody L, Foster B, Petrosino J . Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A. 2012; 109(15):5809-14. PMC: 3326496. DOI: 10.1073/pnas.1120577109. View

Anderson M, Garcia E, Cotter P . The Burkholderia bcpAIOB genes define unique classes of two-partner secretion and contact dependent growth inhibition systems. PLoS Genet. 2012; 8(8):e1002877. PMC: 3415462. DOI: 10.1371/journal.pgen.1002877. View

Klockgether J, Munder A, Neugebauer J, Davenport C, Stanke F, Larbig K . Genome diversity of Pseudomonas aeruginosa PAO1 laboratory strains. J Bacteriol. 2009; 192(4):1113-21. PMC: 2812968. DOI: 10.1128/JB.01515-09. View

Wexler A, Bao Y, Whitney J, Bobay L, Xavier J, Schofield W . Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proc Natl Acad Sci U S A. 2016; 113(13):3639-44. PMC: 4822603. DOI: 10.1073/pnas.1525637113. View

Kelley L, Mezulis S, Yates C, Wass M, Sternberg M . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015; 10(6):845-58. PMC: 5298202. DOI: 10.1038/nprot.2015.053. View

Rosales-Reyes R, Skeldon A, Aubert D, Valvano M . The Type VI secretion system of Burkholderia cenocepacia affects multiple Rho family GTPases disrupting the actin cytoskeleton and the assembly of NADPH oxidase complex in macrophages. Cell Microbiol. 2011; 14(2):255-73. DOI: 10.1111/j.1462-5822.2011.01716.x. View

Lapouge K, Schubert M, Allain F, Haas D . Gac/Rsm signal transduction pathway of gamma-proteobacteria: from RNA recognition to regulation of social behaviour. Mol Microbiol. 2007; 67(2):241-53. DOI: 10.1111/j.1365-2958.2007.06042.x. View

10.

Zimmermann L, Stephens A, Nam S, Rau D, Kubler J, Lozajic M . A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core. J Mol Biol. 2017; 430(15):2237-2243. DOI: 10.1016/j.jmb.2017.12.007. View

11.

Marden J, Diaz M, Walton W, Gode C, Betts L, Urbanowski M . An unusual CsrA family member operates in series with RsmA to amplify posttranscriptional responses in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2013; 110(37):15055-60. PMC: 3773774. DOI: 10.1073/pnas.1307217110. View

12.

Mougous J, Gifford C, Ramsdell T, Mekalanos J . Threonine phosphorylation post-translationally regulates protein secretion in Pseudomonas aeruginosa. Nat Cell Biol. 2007; 9(7):797-803. DOI: 10.1038/ncb1605. View

13.

Mougous J, Cuff M, Raunser S, Shen A, Zhou M, Gifford C . A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science. 2006; 312(5779):1526-30. PMC: 2800167. DOI: 10.1126/science.1128393. View

14.

Jorth P, Staudinger B, Wu X, Hisert K, Hayden H, Garudathri J . Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs. Cell Host Microbe. 2015; 18(3):307-19. PMC: 4589543. DOI: 10.1016/j.chom.2015.07.006. View

15.

Hunt T, Kooi C, Sokol P, Valvano M . Identification of Burkholderia cenocepacia genes required for bacterial survival in vivo. Infect Immun. 2004; 72(7):4010-22. PMC: 427415. DOI: 10.1128/IAI.72.7.4010-4022.2004. View

16.

Radlinski L, Rowe S, Kartchner L, Maile R, Cairns B, Vitko N . Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus. PLoS Biol. 2017; 15(11):e2003981. PMC: 5720819. DOI: 10.1371/journal.pbio.2003981. View

17.

Kordes A, Preusse M, Willger S, Braubach P, Jonigk D, Haverich A . Genetically diverse Pseudomonas aeruginosa populations display similar transcriptomic profiles in a cystic fibrosis explanted lung. Nat Commun. 2019; 10(1):3397. PMC: 6667473. DOI: 10.1038/s41467-019-11414-3. View

18.

Ting S, Bosch D, Mangiameli S, Radey M, Huang S, Park Y . Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins. Cell. 2018; 175(5):1380-1392.e14. PMC: 6239978. DOI: 10.1016/j.cell.2018.09.037. View

19.

Norris M, Kang Y, Wilcox B, Hoang T . Stable, site-specific fluorescent tagging constructs optimized for burkholderia species. Appl Environ Microbiol. 2010; 76(22):7635-40. PMC: 2976199. DOI: 10.1128/AEM.01188-10. View

20.

Russell A, Singh P, Brittnacher M, Bui N, Hood R, Carl M . A widespread bacterial type VI secretion effector superfamily identified using a heuristic approach. Cell Host Microbe. 2012; 11(5):538-49. PMC: 3358704. DOI: 10.1016/j.chom.2012.04.007. View