scholarly journals Distribution of Sigma factors delineates segregation of virulent and avirulent Mycobacterium

2017 ◽  
Author(s):  
Aayatti Mallick Gupta ◽  
Sukhendu Mandal

AbstractSigma factors, in combination with RNA polymerase and several transcription factors play specific role in expression of housekeeping as well as various stress responsive genes in mycobacterial species. The genus Mycobacterium includes a wide range of species under major pathogens, opportunists and non-pathogens. The number and combination of sigma factors is extremely diversified among Mycobacterium. We have performed comparative genome analysis among 40 different species of Mycobacterium whose whole genome sequence is available, in order to identify the distribution of sigma factors. The study illustrate that SigC, SigD, SigG, SigH, SigK and SigI are dominant among the true pathogens. Moreover, 16S rDNA based phylogenetic analyses distinctly differentiate the slow growing Mycobacterium from the fast growers, and clusters the true pathogens from the opportunists and non-pathogens. While evaluating the similarity coefficient upon the allotment of sigma factors of different Mycobacterium species through UPGMA dendrogram analysis, it is apparent that the true pathogens are grouped separately following the similar trend observed from evolutionary approach. Sigma factors playing dominant role in pathogenicity are found stable in nature with high aliphatic index thereby remain flexible at a wide range of temperature. The comparative distribution of six well known virulence factors of Mycobacterium - PhoP, PcaA, FbpA, Mce1B, KatG and PE_PGRS and various sigma factors justify the allotment pattern of mycobacterial sigma factors among pathogenic species. The pathogenicity responsible sigma factors elicit close resemblance with few notable characters of the known virulence factors. Thus the analysis renders that the distribution of sigma factors of different species of Mycobacterium can be a potential tool to predict the pathogenicity index of this genus.

2019 ◽  
Vol 20 (5) ◽  
pp. 1215 ◽  
Author(s):  
Xavier Argemi ◽  
Yves Hansmann ◽  
Kevin Prola ◽  
Gilles Prévost

Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus pathogenicity. In the last decade, numerous CoNS whole-genome sequences have been released, leading to the identification of numerous putative virulence factors. Koch’s postulates and the molecular rendition of these postulates, established by Stanley Falkow in 1988, do not explain the microbial pathogenicity of CoNS. However, whole-genome sequence data has shed new light on CoNS pathogenicity. In this review, we analyzed the contribution of genomics in defining CoNS virulence, focusing on the most frequent and pathogenic CoNS species: S. epidermidis, S. haemolyticus, S. saprophyticus, S. capitis, and S. lugdunensis.


2021 ◽  
Vol 12 (3) ◽  
pp. 698-710
Author(s):  
Peter Rabinowitz ◽  
Bar Zilberman ◽  
Yair Motro ◽  
Marilyn C. Roberts ◽  
Alex Greninger ◽  
...  

Brucellosis has a wide range of clinical severity in humans that remains poorly understood. Whole genome sequencing (WGS) analysis may be able to detect variation in virulence genes. We used Brucella melitensis sequences in the NCBI Sequence Read Archive (SRA) database to assemble 248 whole genomes, and additionally, assembled 27 B. melitensis genomes from samples of human patients in Southern Israel. We searched the 275 assembled genomes for the 43 B. melitensis virulence genes in the Virulence Factors of Pathogenic Bacteria Database (VFDB) and 10 other published putative virulence genes. We explored pan-genome variation across the genomes and in a pilot analysis, explored single nucleotide polymorphism (SNP) variation among the ten putative virulence genes. More than 99% of the genomes had sequences for all Brucella melitensis virulence genes included in the VFDB. The 10 other virulence genes of interest were present across all the genomes, but three of these genes had SNP variation associated with particular Brucella melitensis genotypes. SNP variation was also seen within the Israeli genomes obtained from a small geographic region. While the Brucella genome is highly conserved, this novel and large whole genome study of Brucella demonstrates the ability of whole genome and pan-genome analysis to screen multiple genomes and identify SNP variation in both known and novel virulence genes that could be associated with differential disease virulence. Further development of whole genome techniques and linkage with clinical metadata on disease outcomes could shed light on whether such variation in the Brucella genome plays a role in pathogenesis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ke Huang ◽  
Jianming Tang ◽  
Yong Zou ◽  
Xiangcheng Sun ◽  
Jianbin Lan ◽  
...  

Alternaria alternata is a pathogen in a wide range of agriculture crops and causes significant economic losses. A strain of A. alternata (Y784-BC03) was isolated and identified from “Hongyang” kiwifruit and demonstrated to cause black spot infections on fruits. The genome sequence of Y784-BC03 was obtained using Nanopore MinION technology. The assembled genome is composed of 33,869,130bp (32.30Mb) comprising 10 chromosomes and 11,954 genes. A total of 2,180 virulence factors were predicted to be present in the obtained genome sequence. The virulence factors comprised genes encoding secondary metabolites, including non-host-specific toxins, cell wall-degrading enzymes, and major transcriptional regulators. The predicted gene clusters encoding genes for the biosynthesis and export of secondary metabolites in the genome of Y784-BC03 were associated with non-host-specific toxins, including cercosporin, dothistromin, and versicolorin B. Major transcriptional regulators of different mycotoxin biosynthesis pathways were identified, including the transcriptional regulators, polyketide synthase, P450 monooxygenase, and major facilitator superfamily transporters.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Syed A. K. Shifat Ahmed ◽  
Michelle Rudden ◽  
Sabrina M. Elias ◽  
Thomas J. Smyth ◽  
Roger Marchant ◽  
...  

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI’s) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.


Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Donghoon Kang ◽  
Natalia V. Kirienko

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.


Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 170
Author(s):  
Angela França ◽  
Vânia Gaio ◽  
Nathalie Lopes ◽  
Luís D. R. Melo

Coagulase-negative staphylococci (CoNS) have emerged as major pathogens in healthcare-associated facilities, being S. epidermidis, S. haemolyticus and, more recently, S. lugdunensis, the most clinically relevant species. Despite being less virulent than the well-studied pathogen S. aureus, the number of CoNS strains sequenced is constantly increasing and, with that, the number of virulence factors identified in those strains. In this regard, biofilm formation is considered the most important. Besides virulence factors, the presence of several antibiotic-resistance genes identified in CoNS is worrisome and makes treatment very challenging. In this review, we analyzed the different aspects involved in CoNS virulence and their impact on health and food.


Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 1103-1115 ◽  
Author(s):  
Hongguang Shao ◽  
Zhijian Tu

Abstract A novel transposon named ITmD37E was discovered in a wide range of mosquito species. Sequence analysis of multiple copies in three Aedes species showed similar terminal inverted repeats and common putative TA target site duplications. The ITmD37E transposases contain a conserved DD37E catalytic motif, which is unique among reported transposons of the IS630-Tc1-mariner superfamily. Sequence comparisons and phylogenetic analyses suggest that ITmD37E forms a novel family distinct from the widely distributed Tc1 (DD34E), mariner (DD34D), and pogo (DDxD) families in the IS630-Tc1-mariner superfamily. The inclusion in the phylogenetic analysis of recently reported transposons and transposons uncovered in our database survey provided revisions to previous classifications and identified two additional families, ITmD37D and ITmD39D, which contain DD37D and DD39D motifs, respectively. The above expansion and reorganization may open the doors to the discovery of related transposons in a broad range of organisms and help illustrate the evolution and structure-function relationships among these distinct transposases in the IS630-Tc1-mariner superfamily. The presence of intact open reading frames and highly similar copies in some of the newly characterized transposons suggests recent transposition. Studies of these novel families may add to the limited repertoire of transgenesis and mutagenesis tools for a wide range of organisms, including the medically important mosquitoes.


Antibiotics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 27
Author(s):  
Ekaterina Chernyaeva ◽  
Mikhail Rotkevich ◽  
Ksenia Krasheninnikova ◽  
Alla Lapidus ◽  
Dmitrii E. Polev ◽  
...  

Mycobacterium tuberculosis is a highly studied pathogen due to public health importance. Despite this, problems like early drug resistance, diagnostics and treatment success prediction are still not fully resolved. Here, we analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice and conduct comparative analysis of whole-genome sequence (WGS) for clinical M. tuberculosis strains collected from patients with pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (XPTB) localization. A total of 72 pulmonary and 73 extrapulmonary microbiologically characterized M. tuberculosis isolates were collected from patients from 2007 to 2014 in Russia. Genomic DNA was used for WGS and obtained data allowed identifying major mutations known to be associated with drug resistance to first-line and second-line antituberculous drugs. In some cases previously described mutations were not identified. Using genome-based phylogenetic analysis we identified M. tuberculosis substrains associated with distinctions in the occurrence in PTB vs. XPTB cases. Phylogenetic analyses did reveal M. tuberculosis genetic substrains associated with TB localization. XPTB was associated with Beijing sublineages Central Asia (Beijing CAO), Central Asia Clade A (Beijing A) and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, the XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV was significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates.


1970 ◽  
Vol 46 (4) ◽  
pp. 513-518 ◽  
Author(s):  
V Subhadradevi ◽  
K Asokkumar ◽  
M Umamaheswari ◽  
AT Sivashanmugam ◽  
JR Ushanandhini ◽  
...  

Since ancient times plant as sources of medicinal compounds have continued to play a dominant role in the maintenance of human health. To treat chronic and infectious diseases plants used in traditional medicine contain a wide range of ingredients. In this regard, Cassia auriculata L. (Caesalpiniaceae) is widely used in Ayurvedic medicine as a tonic, astringent and as a remedy for diabetes, conjunctivitis, ulcers, leprosy, skin and liver diseases. The aim of present study was to evaluate the antimicrobial activity of ethanolic extract of Cassia auriculata leaves and flowers (CALE & CAFE). CALE and CAFE exhibited broad spectrum antimicrobial activity against standard strains of Staphylococcus aureus, Escherichia coli and Bacillus subtilis and exhibited no antifungal activity against standard strains of Candida albicans and Aspergillus niger. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) was carried out for CALE and CAFE. The results obtained in the present study indicate that the CALE and CAFE can be a potential source of natural antimicrobial agents. Key words: Cassia auriculata; Antimicrobial activity; Agar well diffusion method. DOI: http://dx.doi.org/10.3329/bjsir.v46i4.9600 BJSIR 2011; 46(4): 513-518


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shingo Nishiki ◽  
Kenichi Lee ◽  
Mizue Kanai ◽  
Shu-ichi Nakayama ◽  
Makoto Ohnishi

AbstractJapan has had a substantial increase in syphilis cases since 2013. However, research on the genomic features of the Treponema pallidum subspecies pallidum (TPA) strains from these cases has been limited. Here, we elucidated the genetic variations and relationships between TPA strains in Japan (detected between 2014 and 2018) and other countries by whole-genome sequencing and phylogenetic analyses, including syphilis epidemiological surveillance data and information on patient sexual orientation. Seventeen of the 20 strains in Japan were SS14- and the remaining 3 were Nichols-lineage. Sixteen of the 17 SS14-lineage strains were classified into previously reported Sub-lineage 1B. Sub-lineage 1B strains in Japan have formed distinct sub-clusters of strains from heterosexuals and strains from men who have sex with men. These strains were closely related to reported TPA strains in China, forming an East-Asian cluster. However, those strains in these countries evolved independently after diverging from their most recent common ancestor and expanded their genetic diversity during the time of syphilis outbreak in each country. The genetic difference between the TPA strains in these countries was characterized by single-nucleotide-polymorphism analyses of their penicillin binding protein genes. Taken together, our results elucidated the detailed phylogenetic features and transmission networks of syphilis.


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