scholarly journals Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent

2019 ◽  
Author(s):  
Daniel Storey ◽  
Alan McNally ◽  
Mia Åstrand ◽  
Joana Sá-Pessoa Graca Santos ◽  
Isabel Rodriguez-Escudero ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Human Health ◽  
Molecular Mechanisms ◽  
Secretion System ◽  
Type Vi Secretion System ◽  
Microbial Antagonism ◽  
Microbial Competition ◽  
Toxic Activity ◽  
Type Vi Secretion ◽  
Resistant Strains

ABSTRACTKlebsiella pneumoniae is recognized as an urgent threat to human health due to the increasing isolation of multidrug resistant strains. Hypervirulent strains are a major concern due to their ability to cause life-threating infections in healthy hosts. The type VI secretion system (T6SS) is widely implicated in microbial antagonism, and it mediates interactions with host eukaryotic cells in some cases. In silico search for genes orthologous to T6SS component genes and T6SS effector genes across 700 K. pneumoniae genomes shows extensive diversity in T6SS genes across the K. pneumoniae species. Temperature, oxygen tension, pH, osmolarity, iron levels, and NaCl regulate the expression of the T6SS encoded by a hypervirulent K. pneumoniae strain. Polymyxins and human defensin 3 also increase the activity of the T6SS. A screen for regulators governing T6SS uncover the correlation between the transcription of the T6SS and the ability to kill E. coli prey. Whereas H-NS represses the T6SS, PhoPQ, PmrAB, Hfq, Fur, RpoS and RpoN positively regulate the T6SS. K. pneumoniae T6SS mediates intra and inter species bacterial competition. This antagonism is only evident when the prey possess an active T6SS. The PhoPQ two component system governs the activation of K. pneumoniae T6SS in bacterial competitions. Mechanistically, PhoQ periplasmic domain, and the acid patch within, is essential to activate K. pneumoniae T6SS. Klebsiella T6SS also mediates anti-fungal competition. We have delineated the contribution of each of the individual VgrGs in microbial competition, and identified VgrG4 as a T6SS effector. Structurally, domain DUF2345 of VgrG4 is sufficient to intoxicate bacteria and yeast. ROS generation mediates the antibacterial effects of VgrG4, and the antitoxin Sel1E protects against the toxic activity of VgrG4. Our findings provide a better understanding of the regulation of the T6SS in bacterial competitions, and place ROS as an early event in microbial competition.AUTHOR SUMMARYKlebsiella pneumoniae has been singled out as an “urgent threat to human health” due to extremely drug resistant strains. Numerous studies investigate the molecular mechanisms underlying antibiotic resistance in K. pneumoniae, while others dissect the virulence strategies of this pathogen. However, there is still limited knowledge on the fitness of Klebsiella in the environment, and particularly the competition of Klebsiella with other species. Here, we demonstrated that Klebsiella exploits the type VI secretion system (T6SS) nanoweapon to kill bacterial competitors and fungi. K. pneumoniae perceives T6SS attacks from bacterial competitors, resulting in retaliation against the aggressive cell. The perception of the attack involved the sensor PhoPQ and led to the up-regulation of the T6SS. We identified one of the toxins deployed by the T6SS to antagonize other microbes, and revealed how Klebsiella protects itself from this toxin. Our findings provide a better understanding of the T6SS role in microbial competition and uncover new aspects on how bacteria regulate T6SS-mediated microbial antagonism.

scholarly journals Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent

2020 ◽  
Vol 16 (3) ◽  
pp. e1007969 ◽  
Author(s):  
Daniel Storey ◽  
Alan McNally ◽  
Mia Åstrand ◽  
Joana sa-Pessoa Graca Santos ◽  
Isabel Rodriguez-Escudero ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Klebsiella Pneumoniae ◽  
Reactive Oxygen ◽  
Secretion System ◽  
Oxygen Species ◽  
Type Vi Secretion System ◽  
Microbial Competition ◽  
Type Vi Secretion

scholarly journals TheVibrio choleraeType VI Secretion System Can Modulate Host Intestinal Mechanics to Displace Commensal Gut Bacteria

2017 ◽  
Author(s):  
Savannah L. Logan ◽  
Jacob Thomas ◽  
Jinyuan Yan ◽  
Ryan P. Baker ◽  
Drew S. Shields ◽  
...  
Keyword(s):  
Secretion System ◽  
Effector Proteins ◽  
Target Cells ◽  
Type Vi Secretion System ◽  
Zebrafish Model ◽  
Microbial Competition ◽  
Aeromonas Veronii ◽  
Type Vi Secretion ◽  
Commensal Strain

AbstractHost-associated microbiota help defend against bacterial pathogens; the mechanisms that pathogens possess to overcome this defense, however, remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogenVibrio choleraeinvades the intestine. The gut microbiota of fish mono-colonized by commensal strainAeromonas veroniiwas displaced byV. choleraeexpressing its Type VI Secretion System (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing ofAeromonas, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident commensal by the host. Deleting an actin crosslinking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakeningV. cholerae′sability to killAeromonas in vitro. Our finding that bacteria can manipulate host physiology to influence inter-microbial competition has implications for both pathogenesis and microbiome engineering.

scholarly journals Incompatibility of Vibrio fischeri Strains during Symbiosis Establishment Depends on Two Functionally Redundant hcp Genes

2019 ◽  
Vol 201 (19) ◽  
Author(s):  
Kirsten R. Guckes ◽  
Andrew G. Cecere ◽  
Nathan P. Wasilko ◽  
Amanda L. Williams ◽  
Katherine M. Bultman ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Vibrio Fischeri ◽  
Secretion System ◽  
Light Organ ◽  
Type Vi Secretion System ◽  
Content Type ◽  
Type Vi Secretion ◽  
Different Strains

ABSTRACT Bacteria that have the capacity to fill the same niche will compete with one another for the space and resources available within an ecosystem. Such competition is heightened among different strains of the same bacterial species. Nevertheless, different strains often inhabit the same host. The molecular mechanisms that impact competition between different strains within the same host are poorly understood. To address this knowledge gap, the type VI secretion system (T6SS), which is a mechanism for bacteria to kill neighboring cells, was examined in the marine bacterium Vibrio fischeri. Different strains of V. fischeri naturally colonize the light organ of the bobtail squid Euprymna scolopes. The genome of FQ-A001, a T6SS-positive strain, features two hcp genes that are predicted to encode identical subunits of the T6SS. Coincubation assays showed that either hcp gene is sufficient for FQ-A001 to kill another strain via the T6SS in vitro. Additionally, induction of hcp expression is sufficient to induce killing activity in an FQ-A001 mutant lacking both hcp genes. Squid colonization assays involving inocula of FQ-A001-derived strains mixed with ES114 revealed that both hcp genes must be deleted for FQ-A001 and ES114 to occupy the same space within the light organ. These experimental results provide insight into the genetic factors necessary for the T6SS of V. fischeri to function in vivo, thereby increasing understanding of the molecular mechanisms that impact strain diversity within a host. IMPORTANCE Different bacterial strains compete to occupy the same niche. The outcome of such competition can be affected by the type VI secretion system (T6SS), an intercellular killing mechanism of bacteria. Here an animal-bacterial symbiosis is used as a platform for study of the genetic factors that promote the T6SS-mediated killing of one strain by another. Identification of the molecular determinants of T6SS function in vivo contributes to the understanding of how different strains interact within a host.

scholarly journals The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway

2020 ◽  
Author(s):  
Hongying Jiao ◽  
Fan Li ◽  
Tietao Wang ◽  
Joey Kuok Hoong Yam ◽  
Liang Yang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Molecular Mechanisms ◽  
Wild Type Strain ◽  
Secretion System ◽  
Signaling Networks ◽  
Diguanylate Cyclase ◽  
Type Vi Secretion System ◽  
Lifestyle Choice ◽  
Type Vi Secretion

In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identifying the molecular mechanisms that govern lifestyle choice in bacteria is very important. Here, we identified a novel cyclic-di-GMP modulator, PrtR, which was shown to repress pyocin production by inhibition of PrtN and activate the Type III secretion system (T3SS) through PtrB. Compared to a wild-type strain or a prtN mutant, the prtR/prtN double mutant exhibited a wrinkly colony and hyperbiofilm phenotype as well as an increase in intracellular c-di-GMP levels. Interestingly, a diguanylate cyclase (DGC) gene, siaD, was repressed by PrtR. Further experiments revealed that PrtR directly interacts with SiaD, and facilitates the accumulation of c-di-GMP in cells. We also demonstrated that PrtR regulates the activity of Gac/Rsm system, thus affecting expression of the T3SS, type VI secretion system (T6SS) and the formation of biofilm. Taken together, the present findings indicate that PrtR, as a c-di-GMP modulator, plays key roles for the adaptation to the opportunistic infection of P. aeruginosa. Additionally, this study revealed a novel mechanism for PrtR-mediated regulation of the lifestyle transition via the Gac/Rsm and c-di-GMP signaling networks.

scholarly journals Virulence Genotype and Clinical Influence of the Type VI Secretion System in Klebsiella Pneumoniae Isolates Causing Bloodstream Infections

2021 ◽  
Author(s):  
Yin Zhang ◽  
Ying Huang
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bloodstream Infection ◽  
Virulence Genes ◽  
Bloodstream Infections ◽  
Secretion System ◽  
The Other ◽  
High Rate ◽  
Type Vi Secretion System ◽  
Type Vi Secretion ◽  
Other Hand

Abstract BackgroundKlebsiella pneumoniae (K. pneumoniae) causes bloodstream infection (BSI), which is responsible for a high rate of morbidity and mortality among different populations. In mainland China, data on the incidence and features of the T6SS gene cluster in K. pneumoniae is currently scarce. As a result, we conducted a prospective investigation to determine the involvement of the type VI secretion system (T6SS) in K. pneumoniae pathogenicity and antibiotic resistance.MethodIn this retrospective analysis, we enrolled 119 individuals who had been diagnosed with K. pneumoniae bloodstream infection and acquired demographic and clinical data from their medical records. The virulence genes rmpA, rmpA2, aerobactin, iroB, hcp, vgrG, and icmF were tested for K1 and K2, antimicrobial susceptibility. T6SS positive strains (N=20) were identified as having icmF, vgrG, and hcp, while T6SS negative strains (N=99) did not manifest the same. In this study, hvKP was defined as rmpA and aerobactin positivity. Five T6SS+ and five T6SS- isolates were chosen for the competition, serum resistance, and biofilm formation experiments to further gain insights regarding the microbiological properties of T6SS+ K. pneumoniae isolates.ResultAmong 119 isolates obtained from patients with BSIs, 20 (16.8%) were T6SS positive K. pneumoniae. T6SS positive strains had four virulence genes and a greater K1 capsular serotypes rate than T6SS negative bacteria. Among hvKP isolates, the T6SS positive rate was substantially greater than the T6SS negative rate (P = 0.001). T6SS-positive K. pneumoniae strains had a lower rate of antimicrobial resistance in comparison to T6SS-negative bacteria. The 30-day mortality in all patients was 23.1%, and 66.7% (26 patients) of them died in the first 7 days of bacteremia onset. The T6SS genotype determined no significant differences in early (7-day) mortality. On the other hand, late mortality among patients with T6SS+ isolates were 10% compared with 37.4% among patients infected by T6SS− strains (P = 0.01). In comparison to T6SS-negative isolates, K. pneumoniae isolates with T6SS-positive might outcompete Escherichia coli. T6SS+ isolates, on the other hand, did not show stronger biofilm-forming activity or a greater survival rate in presence of normal human serum in comparison to T6SS– isolates.ConclusionIndividuals with BSIs were more likely to have T6SS-positive K. pneumoniae. T6SS+ K. pneumoniae strains appeared to be extremely virulent. In T6SS‐containing K. pneumoniae, the system may play a major role in bacterial competition.

scholarly journals Type VI secretion system mutations reduced competitive fitness of classical Vibrio cholerae biotype

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Benjamin Kostiuk ◽  
Francis J. Santoriello ◽  
Laura Diaz-Satizabal ◽  
Fabiana Bisaro ◽  
Kyung-Jo Lee ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Diarrhoeal Disease ◽  
Secretion System ◽  
Type Vi Secretion System ◽  
Genetic Determinants ◽  
Microbial Competition ◽  
Type Vi Secretion ◽  
Pandemic Strains ◽  
El Tor ◽  
Microbial Attack

AbstractThe gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains to microbial attack by non-pandemic strains and subsequently caused 6th pandemic strains to become vulnerable to El Tor biotype V. cholerae intraspecific competition. The chronology of these T6SS-debilitating mutations agrees with the decline of 6th pandemic classical strains and the emergence of 7th pandemic El Tor V. cholerae.

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