scholarly journals Genomics of Atlantic Forest Mycobacteriaceae strains unravels a mobilome diversity with a novel integrative conjugative element and plasmids harbouring T7SS

2020 ◽  
Vol 6 (7) ◽  
Author(s):  
Sergio Mascarenhas Morgado ◽  
Ana Carolina Paulo Vicente

Mobile genetic elements (MGEs) are agents of bacterial evolution and adaptation. Genome sequencing provides an unbiased approach that has revealed an abundance of MGEs in prokaryotes, mainly plasmids and integrative conjugative elements. Nevertheless, many mobilomes, particularly those from environmental bacteria, remain underexplored despite their representing a reservoir of genes that can later emerge in the clinic. Here, we explored the mobilome of the Mycobacteriaceae family, focusing on strains from Brazilian Atlantic Forest soil. Novel Mycolicibacterium and Mycobacteroides strains were identified, with the former ones harbouring linear and circular plasmids encoding the specialized type-VII secretion system (T7SS) and mobility-associated genes. In addition, we also identified a T4SS-mediated integrative conjugative element (ICEMyc226) encoding two T7SSs and a number of xenobiotic degrading genes. Our study uncovers the diversity of the Mycobacteriaceae mobilome, providing the evidence of an ICE in this bacterial family. Moreover, the presence of T7SS genes in an ICE, as well as plasmids, highlights the role of these mobile genetic elements in the dispersion of T7SS.

2015 ◽  
Vol 83 (11) ◽  
pp. 4349-4361 ◽  
Author(s):  
Swati Shah ◽  
Joe R. Cannon ◽  
Catherine Fenselau ◽  
Volker Briken

ABSTRACTThe ESX-5 secretion system ofMycobacterium tuberculosisis important for bacterial virulence and for the secretion of the large PE/PPE protein family, whose genes constitute 10% of theM. tuberculosisgenome. A four-gene region of the ESX-5 system is duplicated three times in theM. tuberculosisgenome, but the functions of these duplicates are unknown. Here we investigated one of these duplicates: the region carrying theesxI,esxJ,ppe15, andpe8genes (ESX-5a). An ESX-5a deletion mutant in the model systemM. marinumbackground was deficient in the secretion of some members of the PE/PPE family of proteins. Surprisingly, we also identified other proteins that are not members of this family, thus expanding the range of ESX-5 secretion substrates. In addition, we demonstrated that ESX-5a is important for the virulence ofM. marinumin the zebrafish model. Furthermore, we showed the role of theM. tuberculosisESX-5a region in inflammasome activation but not host cell death induction, which is different from the case for theM. tuberculosisESX-5 system. In conclusion, the ESX-5a region is nonredundant with its ESX-5 paralog and is necessary for secretion of a specific subset of proteins inM. tuberculosisandM. marinumthat are important for bacterial virulence ofM. marinum. Our findings point to a role for the three ESX-5 duplicate regions in the selection of substrates for secretion via ESX-5, and hence, they provide the basis for a refined model of the molecular mechanism of this type VII secretion system.


2021 ◽  
Author(s):  
Sergio Mascarenhas Morgado ◽  
Ana Carolina Paulo Vicente

The mobilome plays a crucial role in bacterial adaptation and is therefore a starting point to understand and establish the gene flow occurring in the process of bacterial evolution. This is even more so if we consider that the mobilome of environmental bacteria can be the reservoir of genes that may later appear in the clinic. Recently, new genera have been proposed in the family Mycobacteriaceae , including the genus Mycolicibacterium , which encompasses dozens of species of agricultural, biotechnological, clinical and ecological importance, being ubiquitous in several environments. The current scenario in the Mycobacteriaceae mobilome has some bias because most of the characterized mycobacteriophages were isolated using a single host strain, and the few plasmids reported mainly relate to the genus Mycobacterium . To fill in the gaps in these issues, we performed a systematic in silico study of these mobile elements based on 242 available genomes of the genus Mycolicibacterium . The analyses identified 156 putative plasmids (19 conjugative, 45 mobilizable and 92 non-mobilizable) and 566 prophages in 86 and 229 genomes, respectively. Moreover, a contig was characterized by resembling an actinomycete integrative and conjugative element (AICE). Within this diversity of mobile genetic elements, there is a pool of genes associated with several canonical functions, in addition to adaptive traits, such as virulence and resistance to antibiotics and metals (mercury and arsenic). The type-VII secretion system was a common feature in the predicted plasmids, being associated with genes encoding virulent proteins (EsxA, EsxB, PE and PPE). In addition to the characterization of plasmids and prophages of the family Mycobacteriaceae , this study showed an abundance of these genetic elements in a dozen species of the genus Mycolicibacterium .


2014 ◽  
Vol 83 (1) ◽  
pp. 205-213 ◽  
Author(s):  
Amanda Welin ◽  
Halla Björnsdottir ◽  
Malene Winther ◽  
Karin Christenson ◽  
Tudor Oprea ◽  
...  

Upon infection withMycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system,M. tuberculosisreleases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direct biological activity of CFP-10 has been shown, and CFP-10 has been described as a chaperone protein for ESAT-6. We here show that the ESAT-6:CFP-10 complex induces a transient release of Ca2+from intracellular stores in human neutrophils. Surprisingly, CFP-10 rather than ESAT-6 was responsible for triggering the Ca2+response, in a pertussis toxin-sensitive manner, suggesting the involvement of a G-protein-coupled receptor. In line with this, the response was accompanied by neutrophil chemotaxis and activation of the superoxide-producing NADPH-oxidase. Neutrophils were unique among leukocytes in responding to CFP-10, as monocytes and lymphocytes failed to produce a Ca2+signal upon stimulation with theM. tuberculosisprotein. Hence, CFP-10 may contribute specifically to neutrophil recruitment and activation duringM. tuberculosisinfection, representing a novel biological role for CFP-10 in the ESAT-6:CFP-10 complex, beyond the previously described chaperone function.


2018 ◽  
Vol 31 (4) ◽  
Author(s):  
Sally R. Partridge ◽  
Stephen M. Kwong ◽  
Neville Firth ◽  
Slade O. Jensen

SUMMARYStrains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Enterobacterspp., andEscherichia coli), which have become the most problematic hospital pathogens.


2015 ◽  
Vol 59 (9) ◽  
pp. 5260-5266 ◽  
Author(s):  
L. Zamorano ◽  
E. Miró ◽  
C. Juan ◽  
L. Gómez ◽  
G. Bou ◽  
...  

ABSTRACTWe examined the genetic context of 74 acquiredampCgenes and 17 carbapenemase genes from 85 of 640Enterobacteriaceaeisolates collected in 2009. Using S1 pulsed-field gel electrophoresis and Southern hybridization, 37 of 74blaAmpCgenes were located on large plasmids of different sizes belonging to six incompatibility groups. We used sequencing and PCR mapping to investigate the regions flanking the acquiredampCgenes. TheblaCMY-2-like genes were associated with ISEcp1; the surroundingblaDHAgenes were similar toKlebsiella pneumoniaeplasmid pTN60013 associated with IS26and thepspandsapoperons; and theblaACC-1genes were associated with IS26elements inserted into ISEcp1. All of the carbapenemase genes (blaVIM-1,blaIMP-22, andblaIMP-28) were located in class 1 integrons. Therefore, although plasmids are the main cause of the rapid dissemination ofampCgenes amongEnterobacteriaceae, we need to be aware that other mobile genetic elements, such as insertion sequences, transposons, or integrons, can be involved in the mobilization of these genes of chromosomal origin. Additionally, three new integrons (In846 to In848) are described in this study.


2021 ◽  
Vol 70 (10) ◽  
Author(s):  
Alka Hasani ◽  
Saba Ebrahimzadeh ◽  
Fatemeh Hemmati ◽  
Aytak Khabbaz ◽  
Akbar Hasani ◽  
...  

Alteration in the composition of the gut microbiota can lead to a number of chronic clinical diseases. Akkermansia muciniphila is an anaerobic bacteria constituting 3–5% of the gut microbial community in healthy adults. This bacterium is responsible for degenerating mucin in the gut; its scarcity leads to diverse clinical disorders. In this review, we focus on the role of A. muciniphila in diabetes, obesity and atherosclerosis, as well as the use of this bacterium as a next-generation probiotic. In regard to obesity and diabetes, human and animal trials have shown that A. muciniphila controls the essential regulatory system of glucose and energy metabolism. However, the underlying mechanisms by which A. muciniphila alleviates the complications of obesity, diabetes and atherosclerosis are unclear. At the same time, its abundance suggests improved metabolic disorders, such as metabolic endotoxemia, adiposity insulin resistance and glucose tolerance. The role of A. muciniphila is implicated in declining aortic lesions and atherosclerosis. Well-characterized virulence factors, antigens and cell wall extracts of A. muciniphila may act as effector molecules in these diseases. These molecules may provide novel mechanisms and strategies by which this bacterium could be used as a probiotic for the treatment of obesity, diabetes and atherosclerosis.


2021 ◽  
Vol 70 (5) ◽  
Author(s):  
Noa Hurvitz ◽  
Lea Ohana Sarna Cahan ◽  
Itai Gross ◽  
Daniel Grupel ◽  
Orli Megged ◽  
...  

Introduction: Staphylococcus lugdunensis (SL), a tube coagulase negative Staphylococcus , is known to be pathogenic in adults, causing mainly skin infections. Gap Statement: Previous studies assessing SL's role in paediatric populations are sparse and are mainly limited to case reports. Aim: Present the clinical characteristics consistent with SL infections and its putative role as a pathogen in the paediatric population. Methodology: A retrospective multicentre study was conducted in four paediatric medical centres in Israel. Patients with isolates of SL presenting between 2009–2019 were included. Results: SL was isolated from 40 patients. Average (±SD) age at presentation was 5.9 (±6.2) years, with 22 (55 %) being female. Skin, soft tissue and musculoskeletal infections were the most common (n=20, 50%) followed by ear infections (n=13, 32.5%). Five cases of urine isolates and two isolates from blood culture samples were also reported. Skin abscess was the most common infection among skin and soft tissue isolates, reported in 17 children (85%) with SL being the only pathogen in 15 (75%). Otitis media was the most common ear infection accounting for 12 (92%) of all cases with SL as the only isolate reported in 6 (46%). Five cases of SL isolates from urine specimens were reported, all of which with poor growth of bacteria and normal urinalysis. Two cases of SL growth in blood culture were found in children presenting with signs and symptoms consistent with invasive blood stream infection. Conclusions: In the paediatric population, studied infections caused by SL are increasingly observed. The results of this study highlight its role as a pathogen in soft tissue infections and its putative role in otitis media and invasive blood stream infections. However, the role of SL as an uropathogen was not established.


2017 ◽  
Vol 187 (3) ◽  
pp. 558-567 ◽  
Author(s):  
Kara A Moser ◽  
Lixin Zhang ◽  
Ian Spicknall ◽  
Nikolay P Braykov ◽  
Karen Levy ◽  
...  

mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e01234-20
Author(s):  
Kaichao Chen ◽  
Chen Yang ◽  
Ning Dong ◽  
Miaomiao Xie ◽  
Lianwei Ye ◽  
...  

ABSTRACTThe incidence of ciprofloxacin resistance in Salmonella has increased dramatically in the past decade. To track the evolutionary trend of ciprofloxacin resistance-encoding genetic elements during this period, we surveyed the prevalence of Salmonella in food products in Shenzhen, China, during the period of 2012 to 2017 and performed whole-genome sequencing and genetic analysis of 566 ciprofloxacin-resistant clinical Salmonella strains collected during this survey. We observed that target gene mutations have become much less common, with single gyrA mutation currently detectable in Salmonella enterica serovar Typhimurium only. Multiple plasmid-mediated quinolone resistance (PMQR) genes located in the chromosome and plasmids are now frequently detectable in ciprofloxacin-resistant Salmonella strains of various serotypes. Among them, the qnrS1 gene was often harbored by multiple plasmids, with p10k-like plasmids being the most dominant. Importantly, p10k-like plasmids initially were not conjugative but became transmissible with the help of a helper plasmid. Ciprofloxacin resistance due to combined effect of carriage of the qnrS1 gene and other resistance mechanisms is common. In S. Typhimurium, carriage of qnrS1 is often associated with a single gyrA mutation; in other serotypes, combination of qnrS1 and other PMQR genes located in the chromosomal fragment or plasmid is observed. Another major mechanism of ciprofloxacin resistance, mainly observable in S. Derby, involves a chromosomal fragment harboring the qnrS2–aac(6′)lb-cr–oqxAB elements. Intriguingly, this chromosomal fragment, flanked by IS26, could form a circular intermediate and became transferrable. To conclude, the increase in the incidence of various PMQR mobile genetic elements and their interactions with other resistance mechanism contribute to a sharp increase in the prevalence of ciprofloxacin-resistant clinical Salmonella strains in recent years.IMPORTANCE Resistance of nontyphoidal Salmonella to fluoroquinolones such as ciprofloxacin is known to be mediated by target mutations. This study surveyed the prevalence of Salmonella strains recovered from 2,989 food products in Shenzhen, China, during the period 2012 to 2017 and characterized the genetic features of several PMQR gene-bearing plasmids and ciprofloxacin resistance-encoding DNA fragments. The emergence of such genetic elements has caused a shift in the genetic location of ciprofloxacin resistance determinants from the chromosomal mutations to various mobile genetic elements. The distribution of these PMQR plasmids showed that they exhibited high serotype specificity, except for the p10k-like plasmids, which can be widely detected and efficiently transmitted among Salmonella strains of various serotypes by fusing to a new conjugative helper plasmid. The sharp increase in the prevalence of ciprofloxacin resistance in recent years may cause a predisposition to the emergence of multidrug-resistant Salmonella strains and pose huge challenges to public health and infection control efforts.


Microbiology ◽  
2021 ◽  
Author(s):  
Karine Dufresne ◽  
France Daigle

The Salmonella enterica serovar Typhi genome contains 14 putative fimbrial systems. The Std fimbriae belong to the chaperone-usher family and its regulation has not been investigated in S. Typhi. Several regulators of Std were previously identified in the closely related serovar Typhimurium. We hypothesize that regulators of S. Typhimurium may be shared with S. Typhi, but that several other regulators remain to be discovered. Here, we describe the role of more than 50 different candidate regulators on std expression. Three types of regulators were investigated: known regulators in S. Typhimurium, in silico predicted regulators and virulence/metabolic regulators. Expression of std was determined in the regulator mutants and compared with the wild-type strain. Overall, 21 regulator mutations affect std promoter expression. The role of Crp, a newly identified factor for std expression, was further investigated. Crp acted as an activator of std expression on a distal region of the std promoter region. Together, our results demonstrate the major influence of Crp as a novel transcriptional factor on std promoter expression and later production of Std fimbriae in Salmonella .


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