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1.
BMC Genomics ; 21(1): 314, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306949

RESUMO

BACKGROUND: Campylobacter jejuni and Campylobacter coli are major global causes of bacterial gastroenteritis. Whilst several individual colonisation and virulence factors have been identified, our understanding of their role in the transmission, pathogenesis and ecology of Campylobacter has been hampered by the genotypic and phenotypic diversity within C. jejuni and C. coli. Autotransporter proteins are a family of outer membrane or secreted proteins in Gram-negative bacteria such as Campylobacter, which are associated with virulence functions. In this study we have examined the distribution and predicted functionality of the previously described capC and the newly identified, related capD autotransporter gene families in Campylobacter. RESULTS: Two capC-like autotransporter families, designated capC and capD, were identified by homology searches of genomes of the genus Campylobacter. Each family contained four distinct orthologs of CapC and CapD. The distribution of these autotransporter genes was determined in 5829 C. jejuni and 1347 C. coli genomes. Autotransporter genes were found as intact, complete copies and inactive formats due to premature stop codons and frameshift mutations. Presence of inactive and intact autotransporter genes was associated with C. jejuni and C. coli multi-locus sequence types, but for capC, inactivation was independent from the length of homopolymeric tracts in the region upstream of the capC gene. Inactivation of capC or capD genes appears to represent lineage-specific gene decay of autotransporter genes. Intact capC genes were predominantly associated with the C. jejuni ST-45 and C. coli ST-828 generalist lineages. The capD3 gene was only found in the environmental C. coli Clade 3 lineage. These combined data support a scenario of inter-lineage and interspecies exchange of capC and subsets of capD autotransporters. CONCLUSIONS: In this study we have identified two novel, related autotransporter gene families in the genus Campylobacter, which are not uniformly present and exhibit lineage-specific associations and gene decay. The distribution and decay of the capC and capD genes exemplifies the erosion of species barriers between certain lineages of C. jejuni and C. coli, probably arising through co-habitation. This may have implications for the phenotypic variability of these two pathogens and provide opportunity for new, hybrid genotypes to emerge.


Assuntos
Campylobacter coli/genética , Campylobacter jejuni/genética , Deleção de Genes , Sistemas de Secreção Tipo V/classificação , Sistemas de Secreção Tipo V/genética , Fatores de Virulência/classificação , Fatores de Virulência/genética , Campylobacter coli/patogenicidade , Campylobacter jejuni/patogenicidade , Genoma Bacteriano , Filogenia
2.
J Bacteriol ; 201(23)2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501282

RESUMO

Fusobacterium spp. are Gram-negative, anaerobic, opportunistic pathogens involved in multiple diseases, including a link between the oral pathogen Fusobacterium nucleatum and the progression and severity of colorectal cancer. The identification and characterization of virulence factors in the genus Fusobacterium has been greatly hindered by a lack of properly assembled and annotated genomes. Using newly completed genomes from nine strains and seven species of Fusobacterium, we report the identification and corrected annotation of verified and potential virulence factors from the type 5 secreted autotransporter, FadA, and MORN2 protein families, with a focus on the genetically tractable strain F. nucleatum subsp. nucleatum ATCC 23726 and type strain F. nucleatum subsp. nucleatum ATCC 25586. Within the autotransporters, we used sequence similarity networks to identify protein subsets and show a clear differentiation between the prediction of outer membrane adhesins, serine proteases, and proteins with unknown function. These data have identified unique subsets of type 5a autotransporters, which are key proteins associated with virulence in F. nucleatum However, we coupled our bioinformatic data with bacterial binding assays to show that a predicted weakly invasive strain of F. necrophorum that lacks a Fap2 autotransporter adhesin strongly binds human colonocytes. These analyses confirm a gap in our understanding of how autotransporters, MORN2 domain proteins, and FadA adhesins contribute to host interactions and invasion. In summary, we identify candidate virulence genes in Fusobacterium, and caution that experimental validation of host-microbe interactions should complement bioinformatic predictions to increase our understanding of virulence protein contributions in Fusobacterium infections and disease.IMPORTANCEFusobacterium spp. are emerging pathogens that contribute to mammalian and human diseases, including colorectal cancer. Despite a validated connection with disease, few proteins have been characterized that define a direct molecular mechanism for Fusobacterium pathogenesis. We report a comprehensive examination of virulence-associated protein families in multiple Fusobacterium species and show that complete genomes facilitate the correction and identification of multiple, large type 5a secreted autotransporter genes in previously misannotated or fragmented genomes. In addition, we use protein sequence similarity networks and human cell interaction experiments to show that previously predicted noninvasive strains can indeed bind to and potentially invade human cells and that this could be due to the expansion of specific virulence proteins that drive Fusobacterium infections and disease.


Assuntos
Adesinas Bacterianas/genética , Fusobacterium/genética , Fusobacterium/patogenicidade , Genoma Bacteriano , Sistemas de Secreção Tipo V/genética , Fatores de Virulência/genética , Adesinas Bacterianas/classificação , Adesinas Bacterianas/metabolismo , Sequência de Aminoácidos , Aderência Bacteriana , Linhagem Celular , Biologia Computacional/métodos , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Fusobacterium/classificação , Fusobacterium/metabolismo , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/patologia , Expressão Gênica , Gengiva/microbiologia , Gengiva/patologia , Células HCT116 , Humanos , Filogenia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sistemas de Secreção Tipo V/classificação , Sistemas de Secreção Tipo V/metabolismo , Virulência , Fatores de Virulência/classificação , Fatores de Virulência/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-28536673

RESUMO

Initially identified in pathogenic Gram-negative bacteria, the two-partner secretion (TPS) pathway, also known as Type Vb secretion, mediates the translocation across the outer membrane of large effector proteins involved in interactions between these pathogens and their hosts. More recently, distinct TPS systems have been shown to secrete toxic effector domains that participate in inter-bacterial competition or cooperation. The effects of these systems are based on kin vs. non-kin molecular recognition mediated by specific immunity proteins. With these new toxin-antitoxin systems, the range of TPS effector functions has thus been extended from cytolysis, adhesion, and iron acquisition, to genome maintenance, inter-bacterial killing and inter-bacterial signaling. Basically, a TPS system is made up of two proteins, the secreted TpsA effector protein and its TpsB partner transporter, with possible additional factors such as immunity proteins for protection against cognate toxic effectors. Structural studies have indicated that TpsA proteins mainly form elongated ß helices that may be followed by specific functional domains. TpsB proteins belong to the Omp85 superfamily. Open questions remain on the mechanism of protein secretion in the absence of ATP or an electrochemical gradient across the outer membrane. The remarkable dynamics of the TpsB transporters and the progressive folding of their TpsA partners at the bacterial surface in the course of translocation are thought to be key elements driving the secretion process.


Assuntos
Bactérias/metabolismo , Sistemas de Secreção Bacterianos/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Interações Microbianas/fisiologia , Transporte Proteico/fisiologia , Bactérias/patogenicidade , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas da Membrana Bacteriana Externa/fisiologia , Fenômenos Fisiológicos Bacterianos , Sistemas de Secreção Bacterianos/classificação , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/metabolismo , Toxinas Bacterianas/metabolismo , Regulação Bacteriana da Expressão Gênica , Bactérias Gram-Negativas , Proteínas de Membrana Transportadoras/classificação , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/fisiologia , Transporte Proteico/imunologia , Sistemas de Secreção Tipo V/classificação , Sistemas de Secreção Tipo V/genética , Sistemas de Secreção Tipo V/fisiologia
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