MIX and match: mobile T6SS MIX-effectors enhance bacterial fitness.
Ontology highlight
ABSTRACT:
SUBMITTER: Salomon D
PROVIDER: S-EPMC4802749 | biostudies-other | 2016 Jan-Feb
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The type VI secretion system (T6SS) is a transmembrane multiprotein nanomachine employed by many Gram-negative bacterial species to translocate, in a contact-dependent manner, effector proteins into adjacent prokaryotic or eukaryotic cells. Typically, the T6SS gene cluster encodes at least 13 conserved core components for the apparatus assembly and other less conserved accessory proteins and effectors. It functions as a contractile tail machine comprising a TssB/C sheath and an expelled puncturing device consisting of an Hcp tube topped by a spike complex of VgrG and PAAR proteins. Contraction of the sheath propels the tube out of the bacterial cell into a target cell and leads to the injection of toxic proteins. Different bacteria use the T6SS for specific roles according to the niche and versatility of the organism. Effectors are present both as cargo (by non-covalent interactions with one of the core components) or specialized domains (fused to structural components). Although several anti-prokaryotic effectors T6SSs have been studied, recent studies have led to a substantial increase in the number of characterized anti-eukaryotic effectors. Against eukaryotic cells, the T6SS is involved in modifying and manipulating diverse cellular processes that allows bacteria to colonize, survive and disseminate, including adhesion modification, stimulating internalization, cytoskeletal rearrangements and evasion of host innate immune responses.
| S-EPMC7641602 | biostudies-literature
Project description:Bacterial RNA polymerase is composed of a core of subunits (beta, beta', alpha1, alpha2, omega), which have RNA synthesizing activity, and a specificity factor (sigma), which identifies the start of transcription by recognizing and binding to sequences elements within promoter DNA. Four core promoter consensus sequences, the -10 element, the extended -10 (TGn) element, the -35 element, and the UP elements, have been known for many years; the importance of a nontemplate G at position -5 has been recognized more recently. However, the functions of these elements are not the same. The AT-rich UP elements, the -35 elements ((-35)TTGACA(-30)), and the extended -10 ((-15)TGn(-13)) are recognized as double stranded binding elements, whereas the -5 nontemplate G is recognized in the context of single-stranded DNA at the transcription bubble. Furthermore, the -10 element ((-12)TATAAT(-7)) is recognized as both double strand DNA for the T:A bp at position -12 and as nontemplate, single-strand DNA from positions -11 to -7. The single-strand sequences at positions -11 to -7 as well as the -5 contribute to later steps in transcription initiation that involve isomerization of polymerase and separation of the promoter DNA around the transcription start site. Recent work has demonstrated that the double strand elements may be used in various combinations to yield an effective promoter. Thus, while some minimal number of contacts is required for promoter function, polymerase allows the elements to be mixed and matched. Interestingly, which particular elements are used does not appear to fundamentally alter the transcription bubble generated in the stable complex. In this review, we discuss the multiple steps involved in forming a transcriptionally competent polymerase/promoter complex, and we examine what is known about polymerase recognition of core promoter elements. We suggest that considering promoter elements according to their involvement in early (polymerase binding) or later (polymerase isomerization) steps in transcription initiation rather than simply from their match to conventional promoter consensus sequences is a more instructive form of promoter classification.
| S-EPMC2613000 | biostudies-literature
Project description:Major facilitator superfamily (MFS) transport proteins are ubiquitous in the membranes of all living cells, and ?25% of prokaryotic membrane transport proteins belong to this superfamily. The MFS represents the largest and most diverse group of transporters and includes members that are clinically important. A wide range of substrates is transported in many instances actively by transduction of the energy stored in an H(+) electrochemical gradient into a concentration gradient of substrate. MFS transporters are characterized by a deep central hydrophilic cavity surrounded by 12 mostly irregular transmembrane helices. An alternating inverted triple-helix structural symmetry within the N- and C-terminal six-helix bundles suggests that the proteins arose by intragenic multiplication. However, despite similar features, MFS transporters share only weak sequence homology. Here, we show that rearrangement of the structural symmetry motifs in the Escherichia coli fucose permease (FucP) results in remarkable homology to lactose permease (LacY). The finding is supported by comparing the location of 34 point mutations in FucP to the location of mutants in LacY. Furthermore, in contrast to the conventional, linear sequence alignment, homologies between sugar- and H(+)-binding sites in the two proteins are observed. Thus, LacY and FucP likely evolved from primordial helix-triplets that formed functional transporters; however, the functional segments assembled in a different consecutive order. The idea suggests a simple, parsimonious chain of events that may have led to the enormous sequence diversity within the MFS.
| S-EPMC3625355 | biostudies-literature
Project description:One fundamentally important problem for understanding the mechanism of coupling between substrate and H(+) translocation with secondary active transport proteins is the identification and physical localization of residues involved in substrate and H(+) binding. This information is exceptionally difficult to obtain with the Major Facilitator Superfamily (MFS) because of the broad sequence diversity of the members. The MFS is the largest and most diverse group of transporters, many of which are clinically important, and includes members from all kingdoms of life. A wide range of substrates is transported, in many instances against a concentration gradient by transduction of the energy stored in an H(+) electrochemical gradient using symport mechanisms, which are discussed herein. Crystallographic structures of MFS members indicate that a deep central hydrophilic cavity surrounded by 12 mostly irregular transmembrane helices represents a common structural feature. An inverted triple-helix structural symmetry motif within the N- and C-terminal six-helix bundles suggests that the proteins may have arisen by intragenic multiplication. In the work presented here, the triple-helix motifs are aligned in combinatorial fashion so as to detect functionally homologous positions with known atomic structures of MFS members. Substrate and H(+)-binding sites in symporters that transport substrates, ranging from simple ions like phosphate to more complex peptides or disaccharides, are found to be in similar locations. It also appears likely that there is a homologous ordered kinetic mechanism for the H(+)-coupled MFS symporters.
| S-EPMC3864288 | biostudies-literature
Project description:Bacteria utilize type VI secretion system (T6SS) to deliver antibacterial toxins to target co-habiting bacteria. Here, we report that Burkholderia gladioli strain NGJ1 deploys certain T6SS effectors (TseTBg), having both DNase and RNase activities to kill target bacteria. RNase activity is prominent on NGJ1 as well as other bacterial RNA while DNase activity is pertinent to only other bacteria. The associated immunity (TsiTBg) proteins harbor non-canonical helix-turn-helix motifs and demonstrate transcriptional repression activity, similar to the antitoxins of type II toxin-antitoxin (TA) systems. Genome analysis reveals that homologs of TseTBg are either encoded as TA or T6SS effectors in diverse bacteria. Our results indicate that a new ORF (encoding a hypothetical protein) has evolved as a result of operonic fusion of TA type TseTBg homolog with certain T6SS-related genes by the action of IS3 transposable elements. This has potentially led to the conversion of a TA into T6SS effector in Burkholderia. Our study exemplifies that bacteria can recruit toxins of TA systems as T6SS weapons to diversify its arsenal to dominate during inter-bacterial competitions.
| S-EPMC8183406 | biostudies-literature
Project description:Various safe and effective COVID-19 vaccines utilizing different platforms (mRNA, adenovirus vector, inactivated virus-based) are available against SARS-CoV-2 infection. A prime-boost regimen (administration of two doses) is recommended to induce an adequate and sustained immune response. Most of these vaccines follow a homologous regimen (the same type of vaccine as priming and booster doses). However, there is a growing interest in a heterologous prime-boost vaccination regimen to potentially help address concerns posed by fluctuating vaccine supplies, serious adverse effects (anaphylaxis and thromboembolic episodes following adenovirus-based vaccines), new emerging virulent strains, inadequate immune response in immunocompromised individuals, and waning immunity. Various studies have demonstrated that heterologous prime-boost vaccination may induce comparable or higher antibody (spike protein) titers and a similar reactogenicity profile to the homologous prime-boost regimen. Based on these considerations, the Center for Disease Control and Prevention has issued guidance supporting the "mix-and-match" heterologous boost COVID-19 vaccine strategy.
| S-EPMC9326526 | biostudies-literature
Project description:Bacteria utilize type VI secretion system (T6SS) to deliver antibacterial toxins to target co-habiting bacteria. Here we report that Burkholderia gladioli strain NGJ1 deploys certain T6SS effectors (TseTBg), having both DNase and RNase activities to kill target bacteria. RNase activity is prominent on NGJ1 as well as other bacterial RNA while DNase activity is pertinent to only other bacteria. The associated immunity (TsiTBg) proteins harbour non-canonical helix-turn-helix motifs and demonstrate transcriptional repression activity, similar to the antitoxins of type II toxin-antitoxin (TA) systems. Genome analysis reveals that homologs of TseTBg are either encoded as TA or T6SS effectors in diverse bacteria. Our results indicate that a new ORF (encoding a hypothetical protein) has evolved as a result of operonic fusion of TA type TseTBg homolog with certain T6SS related genes by the action of IS3 transposable elements. This has potentially led to the conversion of a TA into T6SS effector in Burkholderia. Our study exemplifies that bacteria can recruit toxins of TA systems as T6SS weapons to diversify its arsenal to dominate during inter-bacterial competitions.
| S-SCDT-EMBOR-2020-51857V1 | biostudies-other
Project description:Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.
| S-EPMC8032392 | biostudies-literature
Project description:The formation of well-defined supramolecular assemblies involves competition between intermolecular and intramolecular interactions, which is quantified by effective molarity. Formation of a duplex between two oligomers equipped with recognition sites displayed along a non-interacting backbone requires that once one intermolecular interaction has been formed, all subsequent interactions take place in an intramolecular sense. The efficiency of this process is governed by the geometric complementarity and conformational flexibility of the backbone linking the recognition sites. Here we report a series of phosphine oxide H-bond acceptor AA 2-mers and phenol H-bond donor DD 2-mers, where the two recognition sites are connected by isomeric backbone modules that vary in geometry and flexibility. All AA and DD combinations form stable AA·DD duplexes, where two cooperative H-bonds lead to an increase in stability of an order of magnitude compared with the corresponding A·D complexes that can only form one H-bond. For all six possible backbone combinations, the effective molarity for duplex formation is approximately constant (7-20 mM). Thus strict complementarity and high degrees of preorganisation are not required for efficient supramolecular assembly. Provided there is some flexibility, quite different backbone modules can be used interchangeably to construct stable H-bonded duplexes.
| S-EPMC5592378 | biostudies-literature
Project description:Gram-negative bacteria deliver effectors via the type VI secretion system (T6SS) to outcompete their rivals. Each bacterial strain carries a different arsenal of effectors; the identities of many remain unknown. Here, we present an approach to identify T6SS effectors encoded in bacterial genomes of interest, without prior knowledge of the effectors' domain content or genetic neighborhood. Our pipeline comprises a comparative genomics analysis followed by screening using a surrogate T6SS+ strain. Using this approach, we identify an antibacterial effector belonging to the T6SS1 of Vibrio parahaemolyticus, representing a widespread family of T6SS effectors sharing a C-terminal domain that we name Tme (Type VI membrane-disrupting effector). Tme effectors function in the periplasm where they intoxicate bacteria by disrupting membrane integrity. We believe our approach can be scaled up to identify additional T6SS effectors in various bacterial genera.
| S-EPMC7046647 | biostudies-literature