scholarly journals The Genome-Sequenced Variant of Campylobacter jejuni NCTC 11168 and the Original Clonal Clinical Isolate Differ Markedly in Colonization, Gene Expression, and Virulence-Associated Phenotypes

2004 ◽  
Vol 186 (2) ◽  
pp. 503-517 ◽  
Author(s):  
Erin C. Gaynor ◽  
Shaun Cawthraw ◽  
Georgina Manning ◽  
Joanna K. MacKichan ◽  
Stanley Falkow ◽  
...  

ABSTRACT The genome sequence of the enteric bacterial pathogen Campylobacter jejuni NCTC 11168 (11168-GS) was published in 2000, providing a valuable resource for the identification of C. jejuni-specific colonization and virulence factors. Surprisingly, the 11168-GS clone was subsequently found to colonize 1-day-old chicks following oral challenge very poorly compared to other strains. In contrast, we have found that the original clinical isolate from which 11168-GS was derived, 11168-O, is an excellent colonizer of chicks. Other marked phenotypic differences were also identified: 11168-O invaded and translocated through tissue culture cells far more efficiently and rapidly than 11168-GS, was significantly more motile, and displayed a different morphology. Serotyping, multiple high-resolution molecular genotyping procedures, and subtractive hybridization did not yield observable genetic differences between the variants, suggesting that they are clonal. However, microarray transcriptional profiling of these strains under microaerobic and severely oxygen-limited conditions revealed dramatic expression differences for several gene families. Many of the differences were in respiration and metabolism genes and operons, suggesting that adaptation to different oxygen tensions may influence colonization potential. This correlates biologically with our observation that anaerobically priming 11168-GS or aerobically passaging 11168-O caused an increase or decrease, respectively, in colonization compared to the parent strain. Expression differences were also observed for several flagellar genes and other less well-characterized genes that may participate in motility. Targeted sequencing of the sigma factors revealed specific DNA differences undetected by the other genomic methods. These observations highlight the capacity of C. jejuni to adapt to multiple environmental niches, the likelihood that this adaptation involves genetic evolution, and provides the first whole-genome molecular exploration of the effect of laboratory culture and storage on colonization and virulence properties of this pathogen.

2004 ◽  
Vol 186 (23) ◽  
pp. 8159-8159 ◽  
Author(s):  
Erin C. Gaynor ◽  
Shaun Cawthraw ◽  
Georgina Manning ◽  
Joanna K. MacKichan ◽  
Stanley Falkow ◽  
...  

2004 ◽  
Vol 186 (9) ◽  
pp. 2880-2890 ◽  
Author(s):  
Isabelle Vallet ◽  
Stephen P. Diggle ◽  
Rachael E. Stacey ◽  
Miguel Cámara ◽  
Isabelle Ventre ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an opportunistic bacterial pathogen which poses a major threat to long-term-hospitalized patients and individuals with cystic fibrosis. The capacity of P. aeruginosa to form biofilms is an important requirement for chronic colonization of human tissues and for persistence in implanted medical devices. Various stages of biofilm formation by this organism are mediated by extracellular appendages, such as type IV pili and flagella. Recently, we identified three P. aeruginosa gene clusters that were termed cup (chaperone-usher pathway) based on their sequence relatedness to the chaperone-usher fimbrial assembly pathway in other bacteria. The cupA gene cluster, but not the cupB or cupC cluster, is required for biofilm formation on abiotic surfaces. In this study, we identified a gene (mvaT) encoding a negative regulator of cupA expression. Such regulatory control was confirmed by several approaches, including lacZ transcriptional fusions, Northern blotting, and transcriptional profiling using DNA microarrays. MvaT also represses the expression of the cupB and cupC genes, although the extent of the regulatory effect is not as pronounced as with cupA. Consistent with this finding, mvaT mutants exhibit enhanced biofilm formation. Although the P. aeruginosa genome contains a highly homologous gene, mvaU, the repression of cupA genes is MvaT specific. Thus, MvaT appears to be an important regulatory component within a complex network that controls biofilm formation and maturation in P. aeruginosa.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hengchun Cao ◽  
Hanxiao Xu ◽  
Chunhui Ning ◽  
Li Xiang ◽  
Qiufang Ren ◽  
...  

Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans around the world. The emergence of bacterial resistance is becoming more serious; therefore, development of new vaccines is considered to be an alternative strategy against drug-resistant pathogen. In this study, we investigated the pangenome of 173 C. jejuni strains and analyzed the phylogenesis and the virulence factor genes. In order to acquire a high-quality pangenome, genomic relatedness was firstly performed with average nucleotide identity (ANI) analyses, and an open pangenome of 8,041 gene families was obtained with the correct taxonomy genomes. Subsequently, the virulence property of the core genome was analyzed and 145 core virulence factor (VF) genes were obtained. Upon functional genomics and immunological analyses, five core VF proteins with high antigenicity were selected as potential core vaccine targets for humans. Furthermore, functional annotations indicated that these proteins are involved in important molecular functions and biological processes, such as adhesion, regulation, and secretion. In addition, transcriptome analysis in human cells and pig intestinal loop proved that these vaccine target genes are important in the virulence of C. jejuni in different hosts. Comprehensive pangenome and relevant animal experiments will facilitate discovering the potential core vaccine targets with improved efficiency in reverse vaccinology. Likewise, this study provided some insights into the genetic polymorphism and phylogeny of C. jejuni and discovered potential vaccine candidates for humans. Prospective development of new vaccines using the targets will be an alternative to the use of antibiotics and prevent the development of multidrug-resistant C. jejuni in humans and even other animals.


2007 ◽  
Vol 75 (4) ◽  
pp. 1994-2003 ◽  
Author(s):  
Robert O. Watson ◽  
Veronica Novik ◽  
Dirk Hofreuter ◽  
María Lara-Tejero ◽  
Jorge E. Galán

ABSTRACT Campylobacter jejuni is a major worldwide cause of enteric illnesses. Adult immunocompetent mice are not susceptible to C. jejuni infection. However, we show here that mice deficient in the adaptor protein myeloid differentiation factor 88 (MyD88), which is required for signaling through most Toll-like receptors, can be stably colonized by C. jejuni but not by isogenic derivatives carrying mutations in known virulence genes. We also found that Nramp1 deficiency increases the mouse susceptibility to C. jejuni infection when administered systemically. These results indicate that MyD88-deficient mice could be a useful model to study C. jejuni colonization and reveal a potential role for Nramp1 in the control of this bacterial pathogen.


2019 ◽  
Vol 20 (10) ◽  
pp. 2472 ◽  
Author(s):  
Lei Dong ◽  
Lei Qin ◽  
Xiuru Dai ◽  
Zehong Ding ◽  
Ran Bi ◽  
...  

The morphological development of the leaf greatly influences plant architecture and crop yields. The maize leaf is composed of a leaf blade, ligule and sheath. Although extensive transcriptional profiling of the tissues along the longitudinal axis of the developing maize leaf blade has been conducted, little is known about the transcriptional dynamics in sheath tissues, which play important roles in supporting the leaf blade. Using a comprehensive transcriptome dataset, we demonstrated that the leaf sheath transcriptome dynamically changes during maturation, with the construction of basic cellular structures at the earliest stages of sheath maturation with a transition to cell wall biosynthesis and modifications. The transcriptome again changes with photosynthesis and lignin biosynthesis at the last stage of sheath tissue maturation. The different tissues of the maize leaf are highly specialized in their biological functions and we identified 15 genes expressed at significantly higher levels in the leaf sheath compared with their expression in the leaf blade, including the BOP2 homologs GRMZM2G026556 and GRMZM2G022606, DOGT1 (GRMZM2G403740) and transcription factors from the B3 domain, C2H2 zinc finger and homeobox gene families, implicating these genes in sheath maturation and organ specialization.


Acta Naturae ◽  
2013 ◽  
Vol 5 (2) ◽  
pp. 62-69 ◽  
Author(s):  
T. A. Skvortsov ◽  
D. V. Ignatov ◽  
K. B. Majorov ◽  
A. S. Apt ◽  
T. L. Azhikina

Whole transcriptome profiling is now almost routinely used in various fields of biology, including microbiology. In vivo transcriptome studies usually provide relevant information about the biological processes in the organism and thus are indispensable for the formulation of hypotheses, testing, and correcting. In this study, we describe the results of genome-wide transcriptional profiling of the major human bacterial pathogen M. tuberculosis during its persistence in lungs. Two mouse strains differing in their susceptibility to tuberculosis were used for experimental infection with M. tuberculosis. Mycobacterial transcriptomes obtained from the infected tissues of the mice at two different time points were analyzed by deep sequencing and compared. It was hypothesized that the changes in the M. tuberculosis transcriptome may attest to the activation of the metabolism of lipids and amino acids, transition to anaerobic respiration, and increased expression of the factors modulating the immune response. A total of 209 genes were determined whose expression increased with disease progression in both host strains (commonly upregulated genes, CUG). Among them, the genes related to the functional categories of lipid metabolism, cell wall, and cell processes are of great interest. It was assumed that the products of these genes are involved in M. tuberculosis adaptation to the host immune system defense, thus being potential targets for drug development.


2020 ◽  
Author(s):  
Elizabeth Heath-Heckman ◽  
Shinja Yoo ◽  
Christopher Winchell ◽  
Maurizio Pellegrino ◽  
James Angstadt ◽  
...  

ABSTRACTWhile leeches in the genus Hirudo have long been models for neurobiology, the molecular underpinnings of nervous system structure and function in this group remain largely unknown. To begin to bridge this gap, we performed RNASeq on pools of identified neurons of the central nervous system (CNS): sensory T (touch), P (pressure) and N (nociception) neurons; neurosecretory Retzius cells; and ganglia from which these four cell types had been removed. Bioinformatic analyses identified 2,812 putative genes whose expression differed significantly among the samples. These genes clustered into 7 groups which could be associated with one or more of the identified cell types. We verified predicted expression patterns through in situ hybridization on whole CNS ganglia, and found that orthologous genes were for the most part similarly expressed in a divergent leech genus, suggesting evolutionarily conserved roles for these genes. Transcriptional profiling allowed us to identify candidate phenotype-defining genes from expanded gene families. Thus, we identified one of eight hyperpolarization-activated cyclic-nucleotide gated (HCN) channels as a candidate for mediating the prominent sag current in P neurons, and found that one of five inositol triphosphate receptors (IP3Rs), representing a sub-family of IP3Rs absent from vertebrate genomes, is expressed with high specificity in T cells. We also identified one of two piezo genes, two of ~65 deg/enac genes, and one of at least 16 transient receptor potential (trp) genes as prime candidates for involvement in sensory transduction in the three distinct classes of leech mechanosensory neurons.


2020 ◽  
Author(s):  
Jeffrey R. Johnson ◽  
Trevor Parry ◽  
Teresa Repasy ◽  
Kristina M. Geiger ◽  
Erik Verschueren ◽  
...  

SUMMARYMacrophages activate robust antimicrobial functions upon engulfing virulent bacteria, yet a wide array of pathogens paradoxically thrive within these innate immune cells. To probe the pathogen-macrophage interface, we used proteomics to comprehensively quantify changes in post-translational modifications (PTMs) of host proteins during infection with three evolutionarily diverse intracellular pathogens: Mycobacterium tuberculosis, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes. Comparing global phosphorylation and ubiquitylation patterns identified extensive reprogramming of cellular pathways during infection, with ubiquitylation patterns revealing unique pathogen-specific molecular response signatures undetectable by transcriptional profiling. Differential PTM changes during infection with attenuated M. tuberculosis cells lacking the ESX-1 virulence determinant revealed extensive modification of phagosome dynamics and antiviral type I interferon activation. We found that M. tuberculosis-mediated activation of the antiviral OASL1-IRF7 pathway promotes bacterial replication, uncovering a new mechanism of virus-bacterial synergy. Our data reveals remarkable specificity in innate cellular responses to complex stimuli and provides a resource for deeper understanding of host-pathogen interactions.


2016 ◽  
Author(s):  
Sebastien Breurec ◽  
Alexis Criscuolo ◽  
Laure Diancourt ◽  
Olaya Rendueles-Garcia ◽  
Mathias Vandenbogaert ◽  
...  

Elizabethkingia anophelis is an emerging pathogen. Genomic analysis of strains from clinical, environmental or mosquito sources is needed to understand the epidemiological emergence of E. anophelis and to uncover genetic elements implicated in antimicrobial resistance, pathogenesis, or niche adaptation. Here, the genomic sequences of two nosocomial isolates that caused neonatal meningitis in Bangui, Central African Republic, were determined and compared with Elizabethkingia isolates from other world regions and sources. Average nucleotide identity firmly confirmed that E. anophelis, E. meningoseptica and E. miricola represent distinct genomic species and led to re-identification of several strains. Phylogenetic analysis of E. anophelis strains revealed several sublineages and demonstrated a single evolutionary origin of African clinical isolates, which carry unique antimicrobial resistance genes acquired by horizontal transfer. The Elizabethkingia genus and the species E. anophelis had pan-genomes comprising respectively 7,801 and 6,880 gene families, underlining their genomic heterogeneity. African isolates were capsulated and carried a distinctive capsular polysaccharide synthesis cluster. A core-genome multilocus sequence typing scheme applicable to all Elizabethkingia isolates was developed, made publicly available (http://bigsdb.web.pasteur.fr/elizabethkingia), and shown to provide useful insights into E. anophelis epidemiology. Furthermore, a clustered regularly interspaced short palindromic repeats (CRISPR) locus was uncovered in E. meningoseptica, E. miricola and in a few E. anophelis strains. CRISPR spacer variation was observed between the African isolates, illustrating the value of CRISPR for strain subtyping. This work demonstrates the dynamic evolution of E. anophelis genomes and provides innovative tools for Elizabethkingia identification, population biology and epidemiology.


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