Dataset Information

Diversity of Contact-Dependent Growth Inhibition Systems of Pseudomonas aeruginosa

ABSTRACT: Contact-dependent growth inhibition (CDI) systems are used in bacterial competition to hinder the growth of neighboring microbes. These systems utilize a two-partner secretion mechanism to display the CdiA exoprotein at the bacterial cell surface. CdiA forms a long filamentous stalk that facilitates binding to a target cell and delivery of a C-terminal toxin (CT) domain. This CT domain is processed and delivered into the cytoplasm of a target cell upon contact. CDI systems also encode a cognate immunity protein (CdiI) that protects siblings and resistant targeted cells from intoxication by high-affinity binding to the CT. CdiA CT domains vary among strains within a species, and many alleles encode enzymatic functions that target nucleic acids. This variation is thought to help drive diversity and adaptation within a species. CdiA diversity is well studied in Escherichia coli and several other bacteria, but little is known about the extent of this diversity in Pseudomonas aeruginosa. The purpose of this review is to highlight the variability that exists in CDI systems of P. aeruginosa. We show that this diversity is apparent even among strains isolated from a single geographical region, suggesting that CDI systems play an important role in the ecology of P. aeruginosa.

SUBMITTER: Allen JP

PROVIDER: S-EPMC6597396 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Diversity of Contact-Dependent Growth Inhibition Systems of <i>Pseudomonas aeruginosa</i>

Allen Jonathan P JP Hauser Alan R AR

Journal of bacteriology 20190621 14

Contact-dependent growth inhibition (CDI) systems are used in bacterial competition to hinder the growth of neighboring microbes. These systems utilize a two-partner secretion mechanism to display the CdiA exoprotein at the bacterial cell surface. CdiA forms a long filamentous stalk that facilitates binding to a target cell and delivery of a C-terminal toxin (CT) domain. This CT domain is processed and delivered into the cytoplasm of a target cell upon contact. CDI systems also encode a cognate ...[more]

PMID: 31036723

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Project description:Microorganisms exist in a diverse ecosystem and have evolved many different mechanisms for sensing and influencing the polymicrobial environment around them, utilizing both diffusible and contact-dependent signals. Contact-dependent growth inhibition (CDI) is one such communication system employed by Gram-negative bacteria. In addition to CDI mediation of growth inhibition, recent studies have demonstrated CDI-mediated control of communal behaviors such as biofilm formation. We postulated that CDI may therefore play an active role in host-pathogen interactions, allowing invading strains to establish themselves at polymicrobial mucosal interfaces through competitive interactions while simultaneously facilitating pathogenic capabilities via CDI-mediated signaling. Here, we show that Pseudomonas aeruginosa produces two CDI systems capable of mediating competition under conditions of growth on a surface or in liquid. Furthermore, we demonstrated a novel role for these systems in contributing to virulence in acute infection models, likely via posttranscriptional regulation of beneficial behaviors. While we did not observe any role for the P. aeruginosa CDI systems in biofilm biogenesis, we did identify for the first time robust CDI-mediated competition during interaction with a mammalian host using a model of chronic respiratory tract infection, as well as evidence that CDI expression is maintained in chronic lung infections. These findings reveal a previously unappreciated role for CDI in host-pathogen interactions and emphasize their importance during infection. IMPORTANCE How bacteria compete and communicate with each other is an increasingly recognized aspect of microbial pathogenesis with a major impact on disease outcomes. Gram-negative bacteria have recently been shown to employ a contact-dependent toxin-antitoxin system to achieve both competition and regulation of their physiology. Here, we show that this system is vital for virulence in acute infection as well as for establishment of chronic infection in the multidrug-resistant pathogen Pseudomonas aeruginosa. Greater understanding of the mechanisms underlying bacterial virulence and infection is important for the development of effective therapeutics in the era of increasing antimicrobial resistance.

Project description:Burkholderia species, including opportunistic pathogens in the Burkholderia cepacia complex (Bcc), have genes to produce contact-dependent growth inhibition (CDI) system proteins. CDI is a phenomenon in which Gram-negative bacteria use the toxic C terminus of a polymorphic surface-exposed exoprotein, BcpA, to inhibit the growth of susceptible bacteria upon direct cell-cell contact. Production of a small immunity protein, BcpI, prevents autoinhibition. Although CDI systems appear widespread in Gram-negative bacteria, their function has been primarily examined in several model species. Here we demonstrate that genes encoding predicted CDI systems in Bcc species exhibit considerable diversity. We also show that Burkholderia multivorans, which causes pulmonary infections in patients with cystic fibrosis, expresses genes that encode two CDI systems, both of which appear distinct from the typical Burkholderia-type CDI system. Each system can mediate intrastrain interbacterial competition and contributes to bacterial adherence. Surprisingly, the immunity-protein-encoding bcpI gene of CDI system 1 could be mutated without obvious deleterious effects. We also show that nonpathogenic Burkholderia thailandensis uses CDI to control B. multivorans growth during coculture, providing one of the first examples of interspecies CDI and suggesting that CDI systems could be manipulated to develop therapeutic strategies targeting Bcc pathogens.IMPORTANCE Competition among bacteria affects microbial colonization of environmental niches and host organisms, particularly during polymicrobial infections. The Bcc is a group of environmental bacteria that can cause life-threatening opportunistic infections in patients who have cystic fibrosis or are immunocompromised. Understanding the mechanisms used by these bacterial pathogens to compete with one another may lead to the development of more effective therapies. Findings presented here demonstrate that a Bcc species, Burkholderia multivorans, produces functional CDI system proteins and that growth of this pathogen can be controlled by CDI system proteins produced by neighboring Burkholderia cells.

Dataset Information

Diversity of Contact-Dependent Growth Inhibition Systems of Pseudomonas aeruginosa

Publications

Diversity of Contact-Dependent Growth Inhibition Systems of <i>Pseudomonas aeruginosa</i>

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