Genome-wide subcellular localization of putative outer membrane and extracellular proteins in Leptospira interrogans serovar Lai genome using bioinformatics approaches

<p>Abstract</p> <p>Background</p> <p>In bacterial pathogens, both cell surface-exposed outer membrane proteins and proteins secreted into the extracellular environment play crucial roles in host-pathogen interaction and pathogenesis. Considerable efforts have been made to identify outer membrane (OM) and extracellular (EX) proteins produced by <it>Leptospira interrogans</it>, which may be used as novel targets for the development of infection markers and leptospirosis vaccines.</p> <p>Result</p> <p>In this study we used a novel computational framework based on combined prediction methods with deduction concept to identify putative OM and EX proteins encoded by the <it>Leptospira interrogans </it>genome. The framework consists of the following steps: (1) identifying proteins homologous to known proteins in subcellular localization databases derived from the "consensus vote" of computational predictions, (2) incorporating homology based search and structural information to enhance gene annotation and functional identification to infer the specific structural characters and localizations, and (3) developing a specific classifier for cytoplasmic proteins (CP) and cytoplasmic membrane proteins (CM) using Linear discriminant analysis (LDA). We have identified 114 putative EX and 63 putative OM proteins, of which 41% are conserved or hypothetical proteins containing sequence and/or protein folding structures similar to those of known EX and OM proteins.</p> <p>Conclusion</p> <p>Overall results derived from the combined computational analysis correlate with the available experimental evidence. This is the most extensive <it>in silico </it>protein subcellular localization identification to date for <it>Leptospira interrogans </it>serovar Lai genome that may be useful in protein annotation, discovery of novel genes and understanding the biology of Leptospira.</p

Intrastrain and interstrain genetic variation within a paralogous gene family in Chlamydia pneumoniae

BACKGROUND: Chlamydia pneumoniae causes human respiratory diseases and has recently been associated with atherosclerosis. Analysis of the three recently published C. pneumoniae genomes has led to the identification of a new gene family (the Cpn 1054 family) that consists of 11 predicted genes and gene fragments. Each member encodes a polypeptide with a hydrophobic domain characteristic of proteins localized to the inclusion membrane. RESULTS: Comparative analysis of this gene family within the published genome sequences provided evidence that multiple levels of genetic variation are evident within this single collection of paralogous genes. Frameshift mutations are found that result in both truncated gene products and pseudogenes that vary among isolates. Several genes in this family contain polycytosine (polyC) tracts either upstream or within the terminal 5' end of the predicted coding sequence. The length of the polyC stretch varies between paralogous genes and within single genes in the three genomes. Sequence analysis of genomic DNA from a collection of 12 C. pneumoniae clinical isolates was used to determine the extent of the variation in the Cpn 1054 gene family. CONCLUSIONS: These studies demonstrate that sequence variability is present both among strains and within strains at several of the loci. In particular, changes in the length of the polyC tract associated with the different Cpn 1054 gene family members are common within each tested C. pneumoniae isolate. The variability identified within this newly described gene family may modulate either phase or antigenic variation and subsequent physiologic diversity within a C. pneumoniae population

Evidence for Host-Bacterial Co-evolution via Genome Sequence Analysis of 480 Thai Mycobacterium tuberculosis Lineage 1 Isolates.

Tuberculosis presents a global health challenge. Mycobacterium tuberculosis is divided into several lineages, each with a different geographical distribution. M. tuberculosis lineage 1 (L1) is common in the high-burden areas in East Africa and Southeast Asia. Although the founder effect contributes significantly to the phylogeographic profile, co-evolution between the host and M. tuberculosis may also play a role. Here, we reported the genomic analysis of 480 L1 isolates from patients in northern Thailand. The studied bacterial population was genetically diverse, allowing the identification of a total of 18 sublineages distributed into three major clades. The majority of isolates belonged to L1.1 followed by L1.2.1 and L1.2.2. Comparison of the single nucleotide variant (SNV) phylogenetic tree and the clades defined by spoligotyping revealed some monophyletic clades representing EAI2_MNL, EAI2_NTM and EAI6_BGD1 spoligotypes. Our work demonstrates that ambiguity in spoligotype assignment could be partially resolved if the entire DR region is investigated. Using the information to map L1 diversity across Southeast Asia highlighted differences in the dominant strain-types in each individual country, despite extensive interactions between populations over time. This finding supported the hypothesis that there is co-evolution between the bacteria and the host, and have implications for tuberculosis disease control

A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages.

Global Mycobacterium tuberculosis population comprises 7 major lineages. The Beijing strains, particularly the ones classified as Modern groups, have been found worldwide, frequently associated with drug resistance, younger ages, outbreaks and appear to be expanding. Here, we report analysis of whole genome sequences of 1170 M. tuberculosis isolates together with their patient profiles. Our samples belonged to Lineage 1-4 (L1-L4) with those of L1 and L2 being equally dominant. Phylogenetic analysis revealed several new or rare sublineages. Differential associations between sublineages of M. tuberculosis and patient profiles, including ages, ethnicity, HIV (human immunodeficiency virus) infection and drug resistance were demonstrated. The Ancestral Beijing strains and some sublineages of L4 were associated with ethnic minorities while L1 was more common in Thais. L2.2.1.Ancestral 4 surprisingly had a mutation that is typical of the Modern Beijing sublineages and was common in Akha and Lahu tribes who have migrated from Southern China in the last century. This may indicate that the evolutionary transition from the Ancestral to Modern Beijing sublineages might be gradual and occur in Southern China, where the presence of multiple ethnic groups might have allowed for the circulations of various co-evolving sublineages which ultimately lead to the emergence of the Modern Beijing strains

Polymorphisms in drug-resistant-related genes shared among drug-resistant and pan-susceptible strains of sequence type 10, Beijing family of Mycobacterium tuberculosis

Mutations in genes involved in drug metabolism have been well-associated with drug resistance. Sequence analysis of known antimycobacterial drug-resistant genes is often used to predict resistance to antibiotics. However, some polymorphisms in such genes may serve a phylogenetic purpose rather than resistance to drugs. The Beijing family of Mycobacterium tuberculosis (MTB) is prevalent worldwide and has been associated with the emergence of multidrug resistance. Sequence type (ST) 10 of the Beijing family is the most predominant in countries like Peru, Taiwan and Thailand. A sequence analysis was performed of 81 previously reported drug-resistant associated genes in multidrug-resistant and pan-susceptible strains of the Beijing family sequence type 10 of MTB. This analysis revealed 10 synonymous and 12 nonsynonymous single nucleotide polymorphisms (SNPs) that are shared by all strains under study. One frameshift mutation was also observed to be common to all. These data might be useful in excluding some observed SNPs in drug-resistant-associated genes of MTB Beijing ST 10 when performing genotypic drug susceptibility assay