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The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

Poulin-Laprade D, Carraro N, Burrus V - Front Microbiol (2015)

Bottom Line: Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described.Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids.Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke , Sherbrooke, QC, Canada.

ABSTRACT
Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

No MeSH data available.


Related in: MedlinePlus

Phylogenetic trees based on alignments of amino acid sequences of SetC/AcaC (A) and SetD/AcaD (B) orthologs. The flagellar transcriptional activator proteins FlhC and FlhD of E. coli (Ec) and Serratia marcescens (Sm) were used as outgroups in phylogenetic analyses. Bootstrap values are indicated when over 80%. The individual scale bars represent genetic distances.
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Figure 4: Phylogenetic trees based on alignments of amino acid sequences of SetC/AcaC (A) and SetD/AcaD (B) orthologs. The flagellar transcriptional activator proteins FlhC and FlhD of E. coli (Ec) and Serratia marcescens (Sm) were used as outgroups in phylogenetic analyses. Bootstrap values are indicated when over 80%. The individual scale bars represent genetic distances.

Mentions: A search for additional FlhCD-like regulators amongst other mobile genetic elements was carried out. Because homologies between SetCD and AcaCD, and the master flagellar activator FlhCD, are very weak, the Pfam HMM profiles for FlhC (PF05280) and FlhD (PF05247) domains are unsuitable to find functional orthologs of SetC/AcaC-like and SetD/AcaD-like activators in bacterial genomes. To solve this problem, we generated new HMM profiles based on alignments of the primary sequence of SetC/AcaC and SetD/AcaD protein orthologs. Screening of the Genbank non-redundant protein sequence database using these new profiles revealed a large number of homologous proteins encoded by diverse types of mobile genetic elements in Enterobacteriaceae and Vibrionaceae. Phylogenetic reconstructions using a representative subset of SetC/AcaC and SetD/AcaD orthologs revealed identical clustering in three distinct families distantly related to FlhC and FlhD: (i) SetC and SetD encoded by SRIs, (ii) AcaC and AcaD encoded by ACPs, (iii) putative proteins encoded by SGI1-like elements, S006 and S007, here renamed SgaC and SgaD (SGI1 activator subunits C and D), (iv) putative proteins encoded by pAQU1-like conjugative plasmids, 208 and 209 that we named AqaD and AqaC (pAQU1 activator subunits C and D), (v) putative proteins encoded by pAsa4, G057 and G056, here renamed AsaC and AsaD (pAsa4 activator subunits C and D; Figure 4). Interestingly, the genes coding for these putative transcriptional regulators are found in a similar genetic context in all cases (Figure 5). They are found in close proximity to a gene coding for a TraG homolog, a component of the conjugative apparatus, a gene coding for putative lysozyme-like protein. and genes coding for homologs of the SrpRM partition system and MobI protein. Further investigation are needed to confirm the functionality of these putative activator complexes regarding the activation of their cognate mobile GIs, and their potential impact on other genetic elements.


The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

Poulin-Laprade D, Carraro N, Burrus V - Front Microbiol (2015)

Phylogenetic trees based on alignments of amino acid sequences of SetC/AcaC (A) and SetD/AcaD (B) orthologs. The flagellar transcriptional activator proteins FlhC and FlhD of E. coli (Ec) and Serratia marcescens (Sm) were used as outgroups in phylogenetic analyses. Bootstrap values are indicated when over 80%. The individual scale bars represent genetic distances.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542580&req=5

Figure 4: Phylogenetic trees based on alignments of amino acid sequences of SetC/AcaC (A) and SetD/AcaD (B) orthologs. The flagellar transcriptional activator proteins FlhC and FlhD of E. coli (Ec) and Serratia marcescens (Sm) were used as outgroups in phylogenetic analyses. Bootstrap values are indicated when over 80%. The individual scale bars represent genetic distances.
Mentions: A search for additional FlhCD-like regulators amongst other mobile genetic elements was carried out. Because homologies between SetCD and AcaCD, and the master flagellar activator FlhCD, are very weak, the Pfam HMM profiles for FlhC (PF05280) and FlhD (PF05247) domains are unsuitable to find functional orthologs of SetC/AcaC-like and SetD/AcaD-like activators in bacterial genomes. To solve this problem, we generated new HMM profiles based on alignments of the primary sequence of SetC/AcaC and SetD/AcaD protein orthologs. Screening of the Genbank non-redundant protein sequence database using these new profiles revealed a large number of homologous proteins encoded by diverse types of mobile genetic elements in Enterobacteriaceae and Vibrionaceae. Phylogenetic reconstructions using a representative subset of SetC/AcaC and SetD/AcaD orthologs revealed identical clustering in three distinct families distantly related to FlhC and FlhD: (i) SetC and SetD encoded by SRIs, (ii) AcaC and AcaD encoded by ACPs, (iii) putative proteins encoded by SGI1-like elements, S006 and S007, here renamed SgaC and SgaD (SGI1 activator subunits C and D), (iv) putative proteins encoded by pAQU1-like conjugative plasmids, 208 and 209 that we named AqaD and AqaC (pAQU1 activator subunits C and D), (v) putative proteins encoded by pAsa4, G057 and G056, here renamed AsaC and AsaD (pAsa4 activator subunits C and D; Figure 4). Interestingly, the genes coding for these putative transcriptional regulators are found in a similar genetic context in all cases (Figure 5). They are found in close proximity to a gene coding for a TraG homolog, a component of the conjugative apparatus, a gene coding for putative lysozyme-like protein. and genes coding for homologs of the SrpRM partition system and MobI protein. Further investigation are needed to confirm the functionality of these putative activator complexes regarding the activation of their cognate mobile GIs, and their potential impact on other genetic elements.

Bottom Line: Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described.Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids.Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke , Sherbrooke, QC, Canada.

ABSTRACT
Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

No MeSH data available.


Related in: MedlinePlus