A single point mutation in a TssB/VipA homolog disrupts sheath formation in the type VI secretion system of<i>Proteus mirabilis</i>

Saak, Christina C.; Zepeda-Rivera, Martha A.; Gibbs, Karine A.

doi:10.1101/152124

Cited by 3 publications

(3 citation statements)

References 65 publications

(60 reference statements)

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“…To confirm that killing is indeed independent of T6SS, we used a P. mirabilis Δ tssM mutant, which is deficient in T6SS-mediated effector delivery. This mutant was generated in the P. mirabilis strain BB2000, which was shown to encode only a single T6SS (14, 46). Wild type BB2000 and the Δ tssM mutant strain reduced the viability of E. coli to the same extent and with the same kinetics (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The T6SS is widely used by Gram-negative species as an intra-and inter-bacterial killing mechanism (5,40,43,46,(57)(58)(59)(60)(61) and represents the only contact-dependent killing mechanism described for P. mirabilis (51). However, activity of P. mirabilis T6SS has only been shown against nonkin clonemates and not against other species (42,62).…”

Section: P Mirabilis Encodes a T3ss (51) T3ss Are Widely Used By Bamentioning

confidence: 99%

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Proteus mirabilisemploys a contact-dependent killing system against competingEnterobacteriaceae

Kiani

Santus

Kiernan

et al. 2021

Preprint

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Many bacterial species encode systems for interference competition with other microorganisms. Some systems are effective without contact (e.g. through secretion of toxins), while other systems (e.g. Type VI secretion system (T6SS)) require direct contact between cells. Here, we provide the initial characterization of a novel contact-dependent competition system for Proteus mirabilis. In neonatal mice, a commensal P. mirabilis strain apparently eliminated commensal Escherichia coli. We replicated the phenotype in vitro and showed that P. mirabilis efficiently reduced viability of several Enterobacteriaceae species, but not Gram-positive species or yeast cells. Importantly, P. mirabilis strains isolated from humans also killed E. coli. Reduction of viability occurred from early stationary phase to 24h of culture and was observed in shaking liquid media as well as on solid media. Killing required contact, but was independent of T6SS, the only contact-dependent killing system described for P. mirabilis. Expression of the killing system was regulated by osmolarity and components secreted into the supernatant. Stationary phase P. mirabilis culture supernatant itself did not kill but was sufficient to induce killing in an exponentially growing co-culture. In contrast, killing was largely prevented in media with low osmolarity. In summary, we provide the initial characterization of a potentially novel interbacterial competition system encoded in P. mirabilis.IMPORTANCEThe study of bacterial competition systems has received significant attention in recent years. These systems collectively shape the composition of complex ecosystems like the mammalian gut. They are also being explored as narrow-spectrum alternatives to specifically eliminate problematic pathogenic species. However, many competition systems that effectively work in vitro do not show strong phenotypes in the gut. Our study was informed by an observation in infant mice. Further in vitro studies confirmed that P. mirabilis was able to kill several Enterobacteriaceae species. This killing system is novel for P. mirabilis and might represent a new function of a known system or even a novel system, as the observed characteristics do not fit with described contact-dependent competition systems. Competition systems are frequently present in multiple Enterobacteriaceae species. If present or transferred into a probiotic, it might be used in the future to reduce blooms of pathogenic Enterobacteriaceae associated with disease.

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Section: Resultsmentioning

confidence: 99%

Section: P Mirabilis Encodes a T3ss (51) T3ss Are Widely Used By Bamentioning

confidence: 99%

Proteus mirabilisemploys a contact-dependent killing system against competingEnterobacteriaceae

Kiani

Santus

Kiernan

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…In a T6SS complex, VipAB/TssBC multimers comprise the outer component of the sheath structure; thus, VipA has been used in multiple systems as a target for visualiza-tion of sheath dynamics through the use of a fluorescentlytagged VipA/TssB fusion constructs [14,29,30], including an IPTG-inducible VipA-GFP expression vector in V. fischeri [7,31]. To visualize T6SS activation dynamics, we grew overnight cultures of wildtype ES401 or FQ-A002 strains harboring the VipA-GFP expression vector to an OD 600 ∼1.5 and spotted them onto an agarose pad supplemented with 0.5 mM IPTG immediately prior to imaging.…”

Section: Quantifying T6ss Activation Dynamics Reveals Strain-specific Differencesmentioning

confidence: 99%

A subcellular biochemical model for T6SS dynamics reveals winning competitive strategies

Lin¹,

Smith

Kanso

et al. 2021

Preprint

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The Type VI secretion system (T6SS) is a broadly distributed interbacterial weapon that can be used to eliminate competing bacterial populations. Although unarmed target populations are typically used to study T6SS function, bacteria most likely encounter other T6SS-armed competitors in nature. The outcome of such battles is not well understood, neither is the connection between the outcomes with the subcellular details of the T6SS. Here, we incorporated new biological data derived from natural competitors of Vibrio fischeri light organ symbionts to build a biochemical model for T6SS function at the single cell level. The model accounts for activation of structure formation, structure assembly, and deployment. By developing an integrated agent-based model (IABM) that incorporates strain-specific T6SS parameters, we replicated outcomes of biological competitions, validating our approach. We used the IABM to isolate and manipulate strain-specific physiological differences between competitors, in a way that is not possible using biological samples, to identify winning strategies for T6SS-armed populations. We found that a tipping point exists where the cost of building more T6SS weapons outweighs their protective ability. Furthermore, we found that competitions between a T6SS-armed population and a unarmed target had different outcomes dependent on the geometry of the battlefield: target cells survived at the edges of a range expansion scenario where unlimited territory could be claimed, while competitions within a confined space, much like the light organ crypts where natural V. fischeri compete, resulted in the rapid elimination of the unarmed competitor.

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Non-cognate immunity proteins provide broader defenses against interbacterial effectors in microbial communities

Knecht

Sirias

Utter

et al. 2023

Preprint

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Dense microbial communities, like the gut and soil microbiomes, are dynamic societies. Bacteria can navigate these environments by deploying proteins (effectors) that alter foreign cells' behavior. Immunity proteins preferentially protect neighboring sibling cells, in contrast to canonical toxin-antitoxin systems. A prevailing hypothesis is that when immunity proteins are bound to specific (cognate) protein partners, it is sufficient to disrupt their function; further, there is little-to-no crosstalk with other (non-cognate) effectors. Here, we build on sporadic reports challenging these hypotheses. We show that immunity proteins from a newly defined protein family can bind and protect against non-cognate PD-(D/E)XK-containing effectors from diverse phyla. We describe the domains essential for binding and function and show that binding alone is insufficient for protective activity. Moreover, we found that these effector and immunity genes co-occur in individual human microbiomes. These results expand the growing repertoire of bacterial protection mechanisms and force us to reconsider how non-cognate interactions impact community structure within complex ecosystems.

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A single point mutation in a TssB/VipA homolog disrupts sheath formation in the type VI secretion system ofProteus mirabilis

Cited by 3 publications

References 65 publications

Proteus mirabilisemploys a contact-dependent killing system against competingEnterobacteriaceae

Proteus mirabilisemploys a contact-dependent killing system against competingEnterobacteriaceae

A subcellular biochemical model for T6SS dynamics reveals winning competitive strategies

Non-cognate immunity proteins provide broader defenses against interbacterial effectors in microbial communities

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