Insights From the Genome Sequence of Mycobacterium paragordonae, a Potential Novel Live Vaccine for Preventing Mycobacterial Infections: The Putative Role of Type VII Secretion Systems for an Intracellular Lifestyle Within Free-Living Environmental Predators

Type VII secretion systems (T7SS) have been identified in Actinobacteria and Firmicutes and have been shown to secrete effector proteins with functions in virulence, host toxicity, and/or interbacterial killing in a few genera. Bioinformatic analysis indicates that isolates of Group B Streptococcus (GBS) encode at least four distinct subtypes of T7SS machinery, three of which encode adjacent putative T7SS effectors with WXG and LXG motifs. However, the function of T7SS in GBS pathogenesis is unknown. Here we assessed the role of the most abundant GBS T7SS subtype during GBS pathogenesis. In a murine model of hematogenous meningitis, mice infected with GBS lacking a functional T7SS or lacking the secreted WXG100 effector EsxA exhibited less mortality, lower bacterial burdens in tissues, and decreased inflammation in the brain compared to mice infected with the parental GBS strain. We further showed that this T7SS induces cytotoxicity in brain endothelium and that EsxA contributes to these cytotoxicity phenotypes in a WXG motif-dependent manner. Finally, we determined that EsxA is a pore-forming protein, thus demonstrating the first role for a non-mycobacterial EsxA homolog in pore formation. This work reveals the importance of a T7SS in host–GBS interactions and has implications for T7SS effector function in other Gram-positive bacteria.

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Genome Sequence of Mycobacterium abscessus Phage phiT46-1

Microbiology Resource Announcements ◽

10.1128/mra.01421-20 ◽

2021 ◽

Vol 10 (2) ◽

Author(s):

Elizabeth D. Amarh ◽

Rebekah M. Dedrick ◽

Rebecca A. Garlena ◽

Daniel A. Russell ◽

Deborah Jacobs-Sera ◽

...

Keyword(s):

Genome Sequence ◽

Mycobacterium Abscessus ◽

Spontaneous Release ◽

Secretion Systems ◽

Content Type ◽

Type Vii Secretion

ABSTRACT Mycobacteriophage phiT46-1 is a newly isolated Mycobacterium phage that was isolated by spontaneous release from Mycobacterium abscessus strain Taiwan-46 and infects M. abscessus strain BWH-C. Phage phiT46-1 is unrelated to previously described mycobacteriophages, has a 52,849-bp genome, and includes a polymorphic toxin-immunity cassette associated with type VII secretion systems.

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The colonisation ofLutzomyia youngiand the putative role of free-living nematodes in the biology of phlebotomine sandfly larvae

Parasite ◽

10.1051/parasite/1997043269 ◽

1997 ◽

Vol 4 (3) ◽

pp. 269-271 ◽

Cited By ~ 2

Author(s):

M. Killick-Kendrick ◽

R. Killick-Kendrick ◽

N. Añez ◽

E. Nieves ◽

J.V. Scorza ◽

...

Keyword(s):

Free Living ◽

Phlebotomine Sandfly ◽

Putative Role

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WhiB5, a Transcriptional Regulator That Contributes to Mycobacterium tuberculosis Virulence and Reactivation

Infection and Immunity ◽

10.1128/iai.06328-11 ◽

2012 ◽

Vol 80 (9) ◽

pp. 3132-3144 ◽

Cited By ~ 35

Author(s):

Stefano Casonato ◽

Axel Cervantes Sánchez ◽

Hirohito Haruki ◽

Monica Rengifo González ◽

Roberta Provvedi ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Chronic Infection ◽

Null Mutant ◽

Wild Type ◽

Secretion Systems ◽

Content Type ◽

Type Vii Secretion ◽

Expression Of Genes ◽

Genes Encoding

ABSTRACTThe proteins belonging to the WhiB superfamily are small global transcriptional regulators typical of actinomycetes. In this paper, we characterize the role of WhiB5, aMycobacterium tuberculosisprotein belonging to this superfamily. A null mutant was constructed inM. tuberculosisH37Rv and was shown to be attenuated during both progressive and chronic mouse infections. Mice infected with the mutant had smaller bacillary burdens in the lungs but a larger inflammatory response, suggesting a role of WhiB5 in immunomodulation. Most interestingly, thewhiB5mutant was not able to resume growth after reactivation from chronic infection, suggesting that WhiB5 controls the expression of genes involved in this process. The mutant was also more sensitive than the wild-type parental strain toS-nitrosoglutathione (GSNO) and was less metabolically active following prolonged starvation, underscoring the importance of GSNO and starvation in development and maintenance of chronic infection. DNA microarray analysis identified 58 genes whose expression is influenced by WhiB5, includingsigM, encoding an alternative sigma factor, and genes encoding the constituents of two type VII secretion systems, namely, ESX-2 and ESX-4.

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Role of Metal-Dependent Regulation of ESX-3 Secretion in Intracellular Survival of Mycobacterium tuberculosis

Infection and Immunity ◽

10.1128/iai.00197-16 ◽

2016 ◽

Vol 84 (8) ◽

pp. 2255-2263 ◽

Cited By ~ 16

Author(s):

Emir Tinaztepe ◽

Jun-Rong Wei ◽

Jenelle Raynowska ◽

Cynthia Portal-Celhay ◽

Victor Thompson ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Cell Envelope ◽

Bacterial Pathogen ◽

Transcriptional Response ◽

Secretion Systems ◽

Content Type ◽

Type Vii Secretion ◽

Significant Difference ◽

Iron And Zinc

More people die every year fromMycobacterium tuberculosisinfection than from infection by any other bacterial pathogen. Type VII secretion systems (T7SS) are used by both environmental and pathogenic mycobacteria to secrete proteins across their complex cell envelope. In the nonpathogenMycobacterium smegmatis, the ESX-1 T7SS plays a role in conjugation, and the ESX-3 T7SS is involved in metal homeostasis. InM. tuberculosis, these secretion systems have taken on roles in virulence, and they also are targets of the host immune response. ESX-3 secretes a heterodimer composed of EsxG (TB9.8) and EsxH (TB10.4), which impairs phagosome maturation in macrophages and is essential for virulence in mice. Given the importance of EsxG and EsxH during infection, we examined their regulation. WithM. tuberculosis, the secretion of EsxG and EsxH was regulated in response to iron and zinc, in accordance with the previously described transcriptional response of theesx-3locus to these metals. While iron regulated theesx-3expression in bothM. tuberculosisandM. smegmatis, there is a significant difference in the dynamics of this regulation. InM. smegmatis, theesx-3locus behaved like other iron-regulated genes such asmbtB. InM. tuberculosis, both iron and zinc modestly repressedesx-3expression. Diminished secretion of EsxG and EsxH in response to these metals altered the interaction ofM. tuberculosiswith macrophages, leading to impaired intracellularM. tuberculosissurvival. Our findings detail the regulatory differences ofesx-3inM. tuberculosisandM. smegmatisand demonstrate the importance of metal-dependent regulation of ESX-3 for virulence inM. tuberculosis.

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Genome Sequence of Mycobacterium abscessus Phage phiT45-1

Microbiology Resource Announcements ◽

10.1128/mra.00155-21 ◽

2021 ◽

Vol 10 (10) ◽

Author(s):

Elizabeth D. Amarh ◽

Christian H. Gauthier ◽

Rebekah M. Dedrick ◽

Rebecca A. Garlena ◽

Daniel A. Russell ◽

...

Keyword(s):

Genome Sequence ◽

Mycobacterium Smegmatis ◽

Mycobacterium Abscessus ◽

Secretion Systems ◽

Content Type ◽

Type Vii Secretion

ABSTRACT Mycobacteriophage phiT45-1 is a newly isolated bacteriophage spontaneously released from Mycobacterium abscessus strain Taiwan-45 that lytically infects M. abscessus strain BWH-C; phiT45-1 also infects M. abscessus ATCC 19977 but not Mycobacterium smegmatis. Phage phiT45-1 has a 43,407-bp genome and carries a polymorphic toxin-immunity cassette associated with type VII secretion systems.

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Differential Expression of Paraburkholderia phymatum Type VI Secretion Systems (T6SS) Suggests a Role of T6SS-b in Early Symbiotic Interaction

Frontiers in Plant Science ◽

10.3389/fpls.2021.699590 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sebastian Hug ◽

Yilei Liu ◽

Benjamin Heiniger ◽

Aurélien Bailly ◽

Christian H. Ahrens ◽

...

Keyword(s):

Root Nodules ◽

Rhizobial Strain ◽

Secretion Systems ◽

Phenotypic Analysis ◽

Free Living ◽

Symbiotic Interaction ◽

Type Vi Secretion ◽

Mutant Strains

Paraburkholderia phymatum STM815, a rhizobial strain of the Burkholderiaceae family, is able to nodulate a broad range of legumes including the agriculturally important Phaseolus vulgaris (common bean). P. phymatum harbors two type VI Secretion Systems (T6SS-b and T6SS-3) in its genome that contribute to its high interbacterial competitiveness in vitro and in infecting the roots of several legumes. In this study, we show that P. phymatum T6SS-b is found in the genomes of several soil-dwelling plant symbionts and that its expression is induced by the presence of citrate and is higher at 20/28°C compared to 37°C. Conversely, T6SS-3 shows homologies to T6SS clusters found in several pathogenic Burkholderia strains, is more prominently expressed with succinate during stationary phase and at 37°C. In addition, T6SS-b expression was activated in the presence of germinated seeds as well as in P. vulgaris and Mimosa pudica root nodules. Phenotypic analysis of selected deletion mutant strains suggested a role of T6SS-b in motility but not at later stages of the interaction with legumes. In contrast, the T6SS-3 mutant was not affected in any of the free-living and symbiotic phenotypes examined. Thus, P. phymatum T6SS-b is potentially important for the early infection step in the symbiosis with legumes.

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Intrinsic role of bacterial secretion systems in phylogenetic niche conservation of Bradyrhizobium spp.

FEMS Microbiology Ecology ◽

10.1093/femsec/fiz165 ◽

2019 ◽

Vol 95 (11) ◽

Cited By ~ 1

Author(s):

Goutam Banerjee ◽

Swarnendu Basak ◽

Tathagato Roy ◽

Pritam Chattopadhyay

Keyword(s):

Multivariate Analysis ◽

Secretion Systems ◽

Free Living ◽

Type Iv ◽

In Silico Study ◽

Bradyrhizobium Sp ◽

Living Root ◽

Bacterial Secretion ◽

Bradyrhizobium Spp

ABSTRACT Bradyrhizobium is a biologically important bacterial genus. Different Bradyrhizobium strains exhibit distinct niche selection like free living, root nodular and stem nodular. The present in-silico study was undertaken to identify the role of bacterial secretome in the phylogenetic niche conservation (PNC) of Bradyrhizobium sp. Analysis was carried out with the publicly available 19 complete genome assembly and annotation reports. A protocol was developed to screen the secretome related genes using three different database, viz. genome, proteome and gene ortholog. This resulted into 139 orthologs that include type secretion systems (T1SS-T6SS) along with flagella (Flg), type IV pili (T4P) and tight adherence (Tad) systems. Multivariate analysis using bacterial secretome was undertaken to find out the role of these secretion systems in PNC. In free living strains, T3SS, T4SS and T6SS were completely absent. Whereas, in the stem nodulating strains, T3SS and T6SS were absent, but T4SS was found to be present. On the other hand, the T3SS was found to be present only in the root-nodulating strains. The present investigation clearly demonstrated a pattern of PNC based on the distribution of secretion system components. To the best of our knowledge, this is the first report on PNC of Bradyrhizobium using the multivariate analysis of secretome.

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Mycosins Are Required for the Stabilization of the ESX-1 and ESX-5 Type VII Secretion Membrane Complexes

mBio ◽

10.1128/mbio.01471-16 ◽

2016 ◽

Vol 7 (5) ◽

Cited By ~ 29

Author(s):

Vincent J. C. van Winden ◽

Roy Ummels ◽

Sander R. Piersma ◽

Connie R. Jiménez ◽

Konstantin V. Korotkov ◽

...

Keyword(s):

Essential Role ◽

Intervention Strategies ◽

Independent Function ◽

Secretion Systems ◽

The Core ◽

Proper Functioning ◽

Type Vii Secretion ◽

Membrane Complex ◽

The Stability

ABSTRACT Pathogenic mycobacteria contain up to five type VII secretion (T7S) systems, ESX-1 to ESX-5. One of the conserved T7S components is the serine protease mycosin (MycP). Strikingly, whereas MycP is essential for secretion, the protease activity of MycP 1 in Mycobacterium tuberculosis has been shown to be dispensable for secretion. The essential role of MycP therefore remains unclear. Here we show that MycP 1 and MycP 5 of M. marinum have similar phenotypes, confirming that MycP has a second unknown function that is essential for its T7S system. To investigate whether this role is related to proper functioning of the T7S membrane complex, we first analyzed the composition of the ESX-1 membrane complex and showed that this complex consists of EccBCDE 1 , similarly to what was previously shown for ESX-5. Surprisingly, while mycosins are not an integral part of these purified core complexes, we noticed that the stability of both the ESX-1 complex and the ESX-5 complex is compromised in the absence of their MycP subunit. Additional interaction studies showed that, although mycosins are not part of the central ESX membrane complex, they loosely associate with this complex. We hypothesize that this MycP association with the core membrane complex is crucial for the integrity and functioning of the T7S machinery. IMPORTANCE Among the major virulence factors of pathogenic mycobacteria are the type VII secretion (T7S) systems. Three of these systems, ESX-1, ESX-3, and ESX-5, have been shown to be crucial for virulence or viability. Here we describe the function of mycosin proteases, which are conserved components within these systems. We show that MycP 1 and MycP 5 have a second, proteolytic-independent function which is essential for the T7S system. We additionally found that this second essential role is related to the stabilization and proper functioning of their respective ESX membrane core complexes. Finally, we found that this is mediated by a loose association of MycP with the complex. Understanding the essential role of mycosins in type VII secretion systems, which play central roles in the virulence and viability of pathogenic mycobacteria, may provide new intervention strategies to treat tuberculosis.

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