Mycobacterium tuberculosis interactome analysis unravels potential pathways to drug resistance.

Abstract:

BACKGROUND:Emergence of drug resistant varieties of tuberculosis is posing a major threat to global tuberculosis eradication programmes. Although several approaches have been explored to counter resistance, there has been limited success due to a lack of understanding of how resistance emerges in bacteria upon drug treatment. A systems level analysis of the proteins involved is essential to gain insights into the routes required for emergence of drug resistance. RESULTS:We derive a genome-scale protein-protein interaction network for Mycobacterium tuberculosis H37Rv from the STRING database, with proteins as nodes and interactions as edges. A set of proteins involved in both intrinsic and extrinsic drug resistance mechanisms are identified from literature. We then compute shortest paths from different drug targets to the set of resistance proteins in the protein-protein interactome, to derive a sub-network relevant to study emergence of drug resistance. The shortest paths are then scored and ranked based on a new scheme that considers (a) drug-induced gene upregulation data, from microarray experiments reported in literature, for the individual nodes and (b) edge-hubness, a network parameter which signifies centrality of a given edge in the network. High-scoring paths identified from this analysis indicate most plausible pathways for the emergence of drug resistance. Different targets appear to have different propensities for four drug resistance mechanisms. A new concept of 'co-targets' has been proposed to counter drug resistance, co-targets being defined as protein(s) that need to be simultaneously inhibited along with the intended target(s), to check emergence of resistance to a given drug. CONCLUSION:The study leads to the identification of possible pathways for drug resistance, providing novel insights into the problem of resistance. Knowledge of important proteins in such pathways enables identification of appropriate 'co-targets', best examples being RecA, Rv0823c, Rv0892 and DnaE1, for drugs targeting the mycolic acid pathway. Insights obtained about the propensity of a drug to trigger resistance will be useful both for more careful identification of drug targets as well as to identify target-co-target pairs, both implementable in early stages of drug discovery itself. This approach is also inherently generic, likely to significantly impact drug discovery.

journal_name

BMC Microbiol

journal_title

BMC microbiology

authors

Raman K,Chandra N

doi

10.1186/1471-2180-8-234

subject

Has Abstract

pub_date

2008-12-23 00:00:00

pages

234

issn

1471-2180

pii

1471-2180-8-234

journal_volume

8

pub_type

杂志文章
  • Salmonella induces prominent gene expression in the rat colon.

    abstract:BACKGROUND:Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmon...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-7-84

    authors: Rodenburg W,Keijer J,Kramer E,Roosing S,Vink C,Katan MB,van der Meer R,Bovee-Oudenhoven IM

    更新日期:2007-09-12 00:00:00

  • Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans.

    abstract:BACKGROUND:Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm for...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-13-257

    authors: Pammi M,Liang R,Hicks J,Mistretta TA,Versalovic J

    更新日期:2013-11-14 00:00:00

  • Phylogeographic evidence of cognate recognition site patterns and transformation efficiency differences in H. pylori: theory of strain dominance.

    abstract:BACKGROUND:Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This pheno...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-13-211

    authors: Maldonado-Contreras A,Mane SP,Zhang XS,Pericchi L,Alarcón T,Contreras M,Linz B,Blaser MJ,Domínguez-Bello MG

    更新日期:2013-09-19 00:00:00

  • Administration of two probiotic strains during early childhood does not affect the endogenous gut microbiota composition despite probiotic proliferation.

    abstract:BACKGROUND:Probiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous gut microb...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-017-1090-7

    authors: Laursen MF,Laursen RP,Larnkjær A,Michaelsen KF,Bahl MI,Licht TR

    更新日期:2017-08-17 00:00:00

  • Correction to: Identification of cholesterol-assimilating actinomycetes strain and application of statistical modeling approaches for improvement of cholesterol oxidase production by Streptomyces anulatus strain NEAE-94.

    abstract::Following publication of the original article [1], the authors reported an error in Fig. 2c. ...

    journal_title:BMC microbiology

    pub_type: 已发布勘误

    doi:10.1186/s12866-020-01791-x

    authors: El-Naggar NE,El-Shweihy NM

    更新日期:2020-04-30 00:00:00

  • Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection.

    abstract:BACKGROUND:Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a ph...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-014-0207-5

    authors: Hamza T,Li B

    更新日期:2014-07-25 00:00:00

  • Variation of growth characteristics of pneumococcus with environmental conditions.

    abstract:BACKGROUND:Pneumococcus is exposed to a variety of temperature and oxygen levels in the upper respiratory tract and as it invades the lung, tissues, and blood. We sought to determine the effect of environmental variability on growth in vitro and to assess variability between strains. We evaluated the effect of temperat...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-019-1671-8

    authors: Tóthpál A,Desobry K,Joshi SS,Wyllie AL,Weinberger DM

    更新日期:2019-12-26 00:00:00

  • Insights into the impact of flhF inactivation on Campylobacter jejuni colonization of chick and mice gut.

    abstract:BACKGROUND:Campylobacter jejuni (C. jejuni) is a leading cause of foodborne gastroenteritis worldwide. This bacterium lacks many of the classical virulence factors, and flagellum-associated persistent colonization has been shown to be crucial for its pathogenesis. The flagellum plays a multifunctional role in C. jejuni...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-018-1318-1

    authors: Ren F,Li X,Tang H,Jiang Q,Yun X,Fang L,Huang P,Tang Y,Li Q,Huang J,Jiao XA

    更新日期:2018-10-22 00:00:00

  • Characterization of a filamentous biofilm community established in a cellulose-fed microbial fuel cell.

    abstract:BACKGROUND:Microbial fuel cells (MFCs) are devices that exploit microorganisms to generate electric power from organic matter. Despite the development of efficient MFC reactors, the microbiology of electricity generation remains to be sufficiently understood. RESULTS:A laboratory-scale two-chamber microbial fuel cell ...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-8-6

    authors: Ishii S,Shimoyama T,Hotta Y,Watanabe K

    更新日期:2008-01-10 00:00:00

  • Comparisons of resistance of CF and non-CF pathogens to hydrogen peroxide and hypochlorous acid oxidants in vitro.

    abstract:BACKGROUND:Cystic fibrosis (CF) lung disease has a unique profile of pathogens predominated by Pseudomonas aeruginosa (PsA) and Staphylococcus aureus (SA). These microorganisms must overcome host immune defense to colonize the CF lungs. Polymorphonuclear neutrophils are a major component of the host defense against bac...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-11-112

    authors: Bonvillain RW,Painter RG,Ledet EM,Wang G

    更新日期:2011-05-20 00:00:00

  • Human milk fungi: environmental determinants and inter-kingdom associations with milk bacteria in the CHILD Cohort Study.

    abstract:BACKGROUND:Fungi constitute an important yet frequently neglected component of the human microbiota with a possible role in health and disease. Fungi and bacteria colonise the infant gastrointestinal tract in parallel, yet most infant microbiome studies have ignored fungi. Milk is a source of diverse and viable bacteri...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-020-01829-0

    authors: Moossavi S,Fehr K,Derakhshani H,Sbihi H,Robertson B,Bode L,Brook J,Turvey SE,Moraes TJ,Becker AB,Mandhane PJ,Sears MR,Khafipour E,Subbarao P,Azad MB

    更新日期:2020-06-05 00:00:00

  • Comparative genomics of Enterococcus spp. isolated from bovine feces.

    abstract:BACKGROUND:Enterococcus is ubiquitous in nature and is a commensal of both the bovine and human gastrointestinal (GI) tract. It is also associated with clinical infections in humans. Subtherapeutic administration of antibiotics to cattle selects for antibiotic resistant enterococci in the bovine GI tract. Antibiotic re...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-017-0962-1

    authors: Beukers AG,Zaheer R,Goji N,Amoako KK,Chaves AV,Ward MP,McAllister TA

    更新日期:2017-03-08 00:00:00

  • Bactericidal activity of PA-824 against Mycobacterium tuberculosis under anaerobic conditions and computational analysis of its novel analogues against mutant Ddn receptor.

    abstract:BACKGROUND:The resurgence of multi-drug resistant tuberculosis (MDR-TB) and HIV associated tuberculosis (TB) are of serious global concern. To contain this situation, new anti-tuberculosis drugs and reduced treatment regimens are imperative. Recently, a nitroimidazole, PA-824, has been shown to be active against both r...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-13-218

    authors: Somasundaram S,Anand RS,Venkatesan P,Paramasivan CN

    更新日期:2013-10-01 00:00:00

  • Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota.

    abstract:BACKGROUND:The microbiota of the mammalian gastrointestinal (GI) tract consists of diverse populations of commensal bacteria that interact with host physiological function. Dysregulating these populations, through exogenous means such as antibiotics or dietary changes, can have adverse consequences on the health of the...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-14-189

    authors: Galley JD,Nelson MC,Yu Z,Dowd SE,Walter J,Kumar PS,Lyte M,Bailey MT

    更新日期:2014-07-15 00:00:00

  • Staphylococcus aureus biofilm formation at the physiologic glucose concentration depends on the S. aureus lineage.

    abstract:BACKGROUND:Since bacteria embedded in biofilms are far more difficult to eradicate than planktonic infections, it would be useful to know whether certain Staphylococcus aureus lineages are especially involved in strong biofilm formation. For this reason, in vitro biofilm formation of 228 clinical S. aureus isolates of ...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-9-229

    authors: Croes S,Deurenberg RH,Boumans ML,Beisser PS,Neef C,Stobberingh EE

    更新日期:2009-10-28 00:00:00

  • Identification of a New Delhi metallo-β-lactamase-4 (NDM-4)-producing Escherichia coli in Italy.

    abstract:BACKGROUND:During June-July 2012, six imipenem-resistant Escherichia coli isolates were isolated from two patients hospitalized in a ward of one large tertiary-care hospital in Genoa, Italy. Genetic features associated with blaNDM-4 gene were investigated. RESULTS:The isolates exhibited the same PFGE profile and a mul...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-14-148

    authors: Coppo E,Del Bono V,Ventura F,Camera M,Orengo G,Viscoli C,Marchese A

    更新日期:2014-06-07 00:00:00

  • Planctomycetes dominate biofilms on surfaces of the kelp Laminaria hyperborea.

    abstract:BACKGROUND:Bacteria belonging to Planctomycetes display several unique morphological and genetic features and are found in a wide variety of habitats on earth. Their ecological roles in these habitats are still poorly understood. Planctomycetes have previously been detected throughout the year on surfaces of the kelp L...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-10-261

    authors: Bengtsson MM,Øvreås L

    更新日期:2010-10-15 00:00:00

  • Special issue on enhancing vector refractoriness to trypanosome infection-foreword.

    abstract:: ...

    journal_title:BMC microbiology

    pub_type:

    doi:10.1186/s12866-018-1279-4

    authors: Abd-Alla AMM,Tsiamis G,Boucias DG

    更新日期:2018-11-23 00:00:00

  • Analysis and comparison of the pan-genomic properties of sixteen well-characterized bacterial genera.

    abstract:BACKGROUND:The increasing availability of whole genome sequences allows the gene or protein content of different organisms to be compared, leading to burgeoning interest in the relatively new subfield of pan-genomics. However, while several studies have analyzed protein content relationships in specific groups of bacte...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-10-258

    authors: Trost B,Haakensen M,Pittet V,Ziola B,Kusalik A

    更新日期:2010-10-13 00:00:00

  • Comparative diversity of microbiomes and Resistomes in beef feedlots, downstream environments and urban sewage influent.

    abstract:BACKGROUND:Comparative knowledge of microbiomes and resistomes across environmental interfaces between animal production systems and urban settings is lacking. In this study, we executed a comparative analysis of the microbiota and resistomes of metagenomes from cattle feces, catch basin water, manured agricultural soi...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-019-1548-x

    authors: Zaheer R,Lakin SM,Polo RO,Cook SR,Larney FJ,Morley PS,Booker CW,Hannon SJ,Van Domselaar G,Read RR,McAllister TA

    更新日期:2019-08-27 00:00:00

  • Release of extracellular ATP by bacteria during growth.

    abstract:BACKGROUND:Adenosine triphosphate (ATP) is used as an intracellular energy source by all living organisms. It plays a central role in the respiration and metabolism, and is the most important energy supplier in many enzymatic reactions. Its critical role as the energy storage molecule makes it extremely valuable to all...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-13-301

    authors: Mempin R,Tran H,Chen C,Gong H,Kim Ho K,Lu S

    更新日期:2013-12-24 00:00:00

  • Comparative transcriptomic and proteomic analyses reveal upregulated expression of virulence and iron transport factors of Aeromonas hydrophila under iron limitation.

    abstract:BACKGROUND:Iron plays important roles in the growth, reproduction and pathogenicity of Aeromonas hydrophila. In this study, we detected and compared the mRNA and protein expression profiles of A. hydrophila under normal and iron restricted medium with 200 μM 2,2-Dipyridyl using RNA Sequencing (RNA-seq) and isobaric tag...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-018-1178-8

    authors: Teng T,Xi B,Chen K,Pan L,Xie J,Xu P

    更新日期:2018-06-04 00:00:00

  • Identification of DNA sequence variation in Campylobacter jejuni strains associated with the Guillain-Barré syndrome by high-throughput AFLP analysis.

    abstract:BACKGROUND:Campylobacter jejuni is the predominant cause of antecedent infection in post-infectious neuropathies such as the Guillain-Barré (GBS) and Miller Fisher syndromes (MFS). GBS and MFS are probably induced by molecular mimicry between human gangliosides and bacterial lipo-oligosaccharides (LOS). This study desc...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-6-32

    authors: Godschalk PC,Bergman MP,Gorkink RF,Simons G,van den Braak N,Lastovica AJ,Endtz HP,Verbrugh HA,van Belkum A

    更新日期:2006-04-04 00:00:00

  • Genetic analysis of the capsule polysaccharide (K antigen) and exopolysaccharide genes in pandemic Vibrio parahaemolyticus O3:K6.

    abstract:BACKGROUND:Pandemic Vibrio parahaemolyticus has undergone rapid changes in both K- and O-antigens, making detection of outbreaks more difficult. In order to understand these rapid changes, the genetic regions encoding these antigens must be examined. In Vibrio cholerae and Vibrio vulnificus, both O-antigen and capsular...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-10-274

    authors: Chen Y,Dai J,Morris JG Jr,Johnson JA

    更新日期:2010-11-02 00:00:00

  • Deregulation of phytoene-β-carotene synthase results in derepression of astaxanthin synthesis at high glucose concentration in Phaffia rhodozyma astaxanthin-overproducing strain MK19.

    abstract:BACKGROUND:A major obstacle to industrial-scale astaxanthin production by the yeast Phaffia rhodozyma is the strong inhibitory effect of high glucose concentration on astaxanthin synthesis. We investigated, for the first time, the mechanism of the regulatory effect of high glucose (> 100 g/L) at the metabolite and tran...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-019-1507-6

    authors: Miao L,Chi S,Wu M,Liu Z,Li Y

    更新日期:2019-06-15 00:00:00

  • A novel PBP3 substitution in Haemophilus influenzae confers reduced aminopenicillin susceptibility.

    abstract:BACKGROUND:Identification and characterization of non-typeable Haemophilus influenzae (NTHi) with reduced susceptibility to β-lactam antibiotics due to mutations in penicillin binding protein 3 (PBP3) is a clinical challenge. We analyzed a blood isolate, NTHi93-57485, that was categorized as aminopenicillin resistant b...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-018-1196-6

    authors: Thegerström J,Matuschek E,Su YC,Riesbeck K,Resman F

    更新日期:2018-05-31 00:00:00

  • Genotyping of Chlamydophila psittaci using a new DNA microarray assay based on sequence analysis of ompA genes.

    abstract:BACKGROUND:The currently used genotyping system for the avian zoonotic pathogen Chlamydophila (C.) psittaci has evolved from serology and is based on ompA sequence variations. It includes seven avian and two non-avian genotypes. Restriction enzyme cleavage of the amplified ompA gene and, less frequently, ompA sequencin...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-8-63

    authors: Sachse K,Laroucau K,Hotzel H,Schubert E,Ehricht R,Slickers P

    更新日期:2008-04-17 00:00:00

  • Novel linear lipopeptide paenipeptin C' binds to lipopolysaccharides and lipoteichoic acid and exerts bactericidal activity by the disruption of cytoplasmic membrane.

    abstract:BACKGROUND:There is an urgent need to develop potent antimicrobials for the treatment of infections caused by antibiotic-resistant bacterial pathogens. Paenipeptin C' (C8-Pat) is a novel linear lipopeptide recently discovered by our group. The objectives of this study were to determine the time-kill kinetics of paenipe...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-018-1381-7

    authors: Moon SH,Huang E

    更新日期:2019-01-08 00:00:00

  • Modelling invasive group A streptococcal disease using bioluminescence.

    abstract:BACKGROUND:The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/s12866-018-1200-1

    authors: Lamb LE,Zhi X,Alam F,Pyzio M,Scudamore CL,Wiles S,Sriskandan S

    更新日期:2018-06-19 00:00:00

  • Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells.

    abstract:BACKGROUND:Atherosclerosis is still the leading cause of death in the western world. Besides known risk factors studies demonstrating Chlamydophila pneumoniae (C. pneumoniae) to be implicated in the progression of the disease, little is known about C. pneumoniae infection dynamics. We investigated whether C. pneumoniae...

    journal_title:BMC microbiology

    pub_type: 杂志文章

    doi:10.1186/1471-2180-8-32

    authors: Marino J,Stoeckli I,Walch M,Latinovic-Golic S,Sundstroem H,Groscurth P,Ziegler U,Dumrese C

    更新日期:2008-02-19 00:00:00