Novel Mycobacteria Antigen 85 Complex Binding Motif on Fibronectin

Kuo, C.J.; Bell, Hannah; Hsieh, Ching Lin; Ptak, Christopher; Chang, Yung-Fu

doi:10.1074/jbc.m111.298687

Cited by 46 publications

(46 citation statements)

References 53 publications

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“…4 and Table 1) (56)(57)(58). To our knowledge, out of the many Fn binding proteins that have been identified, only a few bind the Hep2-40K region (59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

Galloway-Peña

Liang²,

Singh

et al. 2015

J Bacteriol

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fThe WxL domain recently has been identified as a novel cell wall binding domain found in numerous predicted proteins within multiple Gram-positive bacterial species. However, little is known about the function of proteins containing this novel domain. Here, we identify and characterize 6 Enterococcus faecium proteins containing the WxL domain which, by reverse transcription-PCR (RT-PCR) and genomic analyses, are located in three similarly organized operons, deemed WxL loci A, B, and C. Western blotting, electron microscopy, and enzyme-linked immunosorbent assays (ELISAs) determined that genes of WxL loci A and C encode antigenic, cell surface proteins exposed at higher levels in clinical isolates than in commensal isolates. Secondary structural analyses of locus A recombinant WxL domain-containing proteins found they are rich in ␤-sheet structure and disordered segments. Using Biacore analyses, we discovered that recombinant WxL proteins from locus A bind human extracellular matrix proteins, specifically type I collagen and fibronectin. Proteins encoded by locus A also were found to bind to each other, suggesting a novel cell surface complex. Furthermore, bile salt survival assays and animal models using a mutant from which all three WxL loci were deleted revealed the involvement of WxL operons in bile salt stress and endocarditis pathogenesis. In summary, these studies extend our understanding of proteins containing the WxL domain and their potential impact on colonization and virulence in E. faecium and possibly other Gram-positive bacterial species. Enterococcus faecium is one of the "no ESKAPE" pathogens responsible for a considerable percentage of nosocomial infections; its ability to cause life-threatening infections and resistance to antibiotics cause considerable difficulties for patients and physicians (1). To date, many of the potential virulence determinants that have been described in E. faecium are MSCRAMMs (microbial surface components recognizing adhesive matrix molecules); these include adhesins or pili anchored to the cell surface by an LPxTG-like motif and contain IgG-like folds (2). Our group previously performed a bioinformatic search for novel surface proteins that might be virulence factors in the E. faecium endocarditis strain TX16 (also known as DO) (3). During this search, we identified a locus which included predicted proteins possessing the previously described WxL domain colocated with a predicted LPxTG-like protein (Fms6) (3, 4).The WxL domain is comprised of several conserved residues along with a highly conserved YXXX(L/I/V)TWXLXXXP motif and a second WxL proximal motif in the last ϳ120 to 190 C-terminal residues of a protein (4,5). Genes encoding proteins with the WxL domain were first described in Lactobacillus plantarum as part of a novel gene cluster found in a subset of low-GϩC-content Gram-positive bacterial species, one of which is E. faecium (6, 7). Bioinformatics and transcriptome data in L. plantarum predicted these loci form cell surface protein complexes involved in ca...

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“…4 and Table 1) (56)(57)(58). To our knowledge, out of the many Fn binding proteins that have been identified, only a few bind the Hep2-40K region (59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

Galloway-Peña

Liang²,

Singh

et al. 2015

J Bacteriol

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“…paratuberculosis like in other mycobacteria (47). Recently, the interaction of Ag85 complex with fibronectin was characterized in molecular detail by measuring dissociation constants and through peptide inhibition assays (36). The investigators identified the 10-amino-acid region within a 40-kDa domain of fibronectin that specifically binds Ag85B.…”

Section: Mycobacterial Proteins Involved In Invasionmentioning

confidence: 99%

“…This 220-kDa host protein consists of 5 well-defined domains of which the 40-kDa domain interacts directly with M. avium subsp. paratuberculosis (36). While M. avium subsp.…”

Section: Host Involvement Enhances Invasionmentioning

confidence: 99%

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No Holes Barred: Invasion of the Intestinal Mucosa by Mycobacterium avium subsp. paratuberculosis

Bannantine

Bermudez

2013

Infect Immun

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The infection biology of Mycobacterium avium subsp. paratuberculosis has recently crystallized, with added details surrounding intestinal invasion. The involvement of pathogen-derived effector proteins such as the major membrane protein, oxidoreductase, and fibronectin attachment proteins have been uncovered. Mutations constructed in this pathogen have also shed light on genes needed for invasion. The host cell types that are susceptible to invasion have been defined, along with their transcriptional response. Recent details have given a new appreciation for the dynamic interplay between the host and bacterium that occurs at the outset of infection. An initial look at the global expression pathways of the host has shown a circumvention of the cell communication pathway by M. avium subsp. paratuberculosis, which loosens the integrity of the tight junctions. We now know that M. avium subsp. paratuberculosis activates the epithelial layer and also actively recruits macrophages to the site of infection. These notable findings are summarized along with added mechanistic details of the early infection model. We conclude by proposing critical next steps to further elucidate the process of M. avium subsp. paratuberculosis invasion.

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“…Streptococcus pneumoniae uses the surface-exposed bacterial protein PspC to facilitate adhesion to the host cell surface by interacting with vitronectin, a host glycoprotein (9). Several mycobacterial proteins that facilitate adhesion to the host epithelial cell membrane, such as fibronectin attachment proteins (FAP), histone-like protein (Hlp), the heparin-binding hemagglutinin (HBHA), and antigen 85, have been characterized (10)(11)(12)(13). Pathogens also take advantage of surface-exposed cytoskeletal proteins for successful adhesion and invasion of epithelial cells.…”

mentioning

confidence: 99%

The Environment of “Mycobacterium avium subsp. hominissuis” Microaggregates Induces Synthesis of Small Proteins Associated with Efficient Infection of Respiratory Epithelial Cells

et al. 2015

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"Mycobacterium avium subsp. hominissuis" is an opportunistic environmental pathogen that causes respiratory illness in immunocompromised patients, such as those with cystic fibrosis as well as other chronic respiratory diseases. Currently, there is no efficient approach to prevent or treat M. avium subsp. hominissuis infection in the lungs. During initial colonization of the airways, M. avium subsp. hominissuis forms microaggregates composed of 3 to 20 bacteria on human respiratory epithelial cells, which provides an environment for phenotypic changes leading to efficient mucosal invasion in vitro and in vivo. DNA microarray analysis was employed to identify genes associated with the microaggregate phenotype. The gene encoding microaggregatebinding protein 1 (MBP-1) (MAV_3013) is highly expressed during microaggregate formation. When expressed in noninvasive Mycobacterium smegmatis, MBP-1 increased the ability of the bacteria to bind to HEp-2 epithelial cells. Using anti-MBP-1 immune serum, microaggregate binding to HEp-2 cells was significantly reduced. By far-Western blotting, and verified by coimmunoprecipitation, we observed that MBP-1 interacts with the host cytoskeletal protein vimentin. As visualized by confocal microscopy, microaggregates, as well as MBP-1, induced vimentin polymerization at the site of bacterium-host cell contact. Binding of microaggregates to HEp-2 cells was inhibited by treatment with an antivimentin antibody, suggesting that MBP-1 expression is important for M. avium subsp. hominissuis adherence to the host cell. MBP-1 immune serum significantly inhibited M. avium subsp. hominissuis infection throughout the respiratory tracts of mice. This study characterizes a pathogenic mechanism utilized by M. avium subsp. hominissuis to bind and invade the host respiratory epithelium, suggesting new potential targets for the development of antivirulence therapy. " M ycobacterium avium subsp. hominissuis" is an environmental bacterium ubiquitous in soil and natural water sources. In addition, M. avium subsp. hominissuis is an opportunistic pathogen that poses a major risk to immunocompromised patients, such as those with HIV infection, cystic fibrosis, and chronic respiratory diseases such as bronchiectasis and chronic obstructive pulmonary diseases (COPD). During the AIDS epidemic, mycobacterial infections became a widespread medical concern due to high morbidity and mortality in severely immunocompromised individuals (1). In recent years, there has been a significant increase in the incidence of nontuberculous mycobacterial (NTM) lung infections, including in cystic fibrosis patients, where M. avium subsp. hominissuis accounts for 72% of mycobacterial infections (2-4). Studies have also found an increase in NTM lung infections in middle-aged women with no known underlying conditions (5).Due to the hardy cell wall of M. avium subsp. hominissuis and its natural resistance to many antibiotics, treatment is lengthy and encompasses a combination of various antibiotics, such as macrolides and ethambut...

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Novel Mycobacteria Antigen 85 Complex Binding Motif on Fibronectin

Cited by 46 publications

References 53 publications

The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

No Holes Barred: Invasion of the Intestinal Mucosa by Mycobacterium avium subsp. paratuberculosis

The Environment of “Mycobacterium avium subsp. hominissuis” Microaggregates Induces Synthesis of Small Proteins Associated with Efficient Infection of Respiratory Epithelial Cells

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