Heparin-binding hemagglutinin (HBHA) of<i>Mycobacterium leprae</i>is expressed during infection and enhances bacterial adherence to epithelial cells

Lima, Cristiana Soares de; Marques, Maria Angela M.; Debrie, Anne-Sophie; Almeida, Elza; Silva, Carlos A.M.; Brennan, Patrick J.; Sarno, Euzenir Nunes; Menozzi, Franco D.; Pessolani, Maria Cristina Vidal

doi:10.1111/j.1574-6968.2009.01488.x

Cited by 28 publications

(16 citation statements)

References 25 publications

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“…Hlp and HBHA are well known as extracellular matrixbinding proteins. While HBHA binds heparan sulfate (13,20), Hlp has been described as a multifunctional adhesin able to interact with laminin, hyaluronic acid, heparan sulfate, and collagen (14,53,(71)(72)(73). Previous studies have shown the in vivo expression of both proteins by M. leprae (62,71).…”

Section: Discussionmentioning

confidence: 99%

“…leprae Hlp and HBHA can mediate mycobacterial entry into epithelial cells. Two mycobacterial proteins, HBHA and Hlp, have been intensely studied and shown to mediate bacterial adhesion to epithelial cells (13,20,53). Since we confirmed by proteomic data that HBHA and Hlp are surface-exposed proteins in M. leprae, we investigated whether recombinant M. leprae proteins would be able to bind to A549 and RPMI 2650 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The recombinant M. leprae proteins heparin-binding hemagglutinin (HBHA) and histone-like protein (Hlp) were obtained as described previously (20,21). Red polystyrene fluorescent beads (1.0 m diameter) were coated with recombinant M. leprae Hlp (50 g/ml), M. leprae HBHA (50 g/ml), or BSA (50 g/ml) for 3 h at RT in 0.2 M carbonate-bicarbonate buffer (pH 9.6).…”

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confidence: 99%

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Interaction of Mycobacterium leprae with Human Airway Epithelial Cells: Adherence, Entry, Survival, and Identification of Potential Adhesins by Surface Proteome Analysis

et al. 2013

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f This study examined the in vitro interaction between Mycobacterium leprae, the causative agent of leprosy, and human alveolar and nasal epithelial cells, demonstrating that M. leprae can enter both cell types and that both are capable of sustaining bacterial survival. Moreover, delivery of M. leprae to the nasal septum of mice resulted in macrophage and epithelial cell infection in the lung tissue, sustaining the idea that the airways constitute an important M. leprae entry route into the human body. Since critical aspects in understanding the mechanisms of infection are the identification and characterization of the adhesins involved in pathogen-host cell interaction, the nude mouse-derived M. leprae cell surface-exposed proteome was studied to uncover potentially relevant adhesin candidates. A total of 279 cell surface-exposed proteins were identified based on selective biotinylation, streptavidin-affinity purification, and shotgun mass spectrometry; 11 of those proteins have been previously described as potential adhesins. In vitro assays with the recombinant forms of the histone-like protein (Hlp) and the heparin-binding hemagglutinin (HBHA), considered to be major mycobacterial adhesins, confirmed their capacity to promote bacterial attachment to epithelial cells. Taking our data together, they suggest that the airway epithelium may act as a reservoir and/or portal of entry for M. leprae in humans. Moreover, our report sheds light on the potentially critical adhesins involved in M. leprae-epithelial cell interaction that may be useful in designing more effective tools for leprosy control.

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Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Interaction of Mycobacterium leprae with Human Airway Epithelial Cells: Adherence, Entry, Survival, and Identification of Potential Adhesins by Surface Proteome Analysis

et al. 2013

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“…It is noteworthy that the TadA homolog HbhA is found in both pathogenic and nonpathogenic mycobacteria and has previously been shown to act as a virulence factor in Mycobacterium tuberculosis and Mycobacterium leprae, for which it is believed to promote dissemination during early stages of infection (13,30). Interestingly, M. tuberculosis has been shown to accumulate TAG and store it in conspicuous inclusion bodies, similar to those seen for Rhodococcus (12,19,20).…”

Section: Vol 76 2010mentioning

confidence: 96%

The Rhodococcus opacus PD630 Heparin-Binding Hemagglutinin Homolog TadA Mediates Lipid Body Formation

MacEachran¹,

Prophete²,

Sinskey

2010

Appl Environ Microbiol

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Generally, prokaryotes store carbon as polyhydroxyalkanoate, starch, or glycogen. The Gram-positive actinomycete Rhodococcus opacus strain PD630 is noteworthy in that it stores carbon in the form of triacylglycerol (TAG). Several studies have demonstrated that R. opacus PD630 can accumulate up to 76% of its cell dry weight as TAG when grown under nitrogen-limiting conditions. While this process is well studied, the underlying molecular and biochemical mechanisms leading to TAG biosynthesis and subsequent storage are poorly understood. We designed a high-throughput genetic screening to identify genes and their products required for TAG biosynthesis and storage in R. opacus PD630. We identified a gene predicted to encode a putative heparin-binding hemagglutinin homolog, which we have termed tadA (triacylglycerol accumulation deficient), as being important for TAG accumulation. Kinetic studies of TAG accumulation in both the wild-type (WT) and mutant strains demonstrated that the tadA mutant accumulates 30 to 40% less TAG than the parental strain (WT). We observed that lipid bodies formed by the mutant strain were of a different size and shape than those of the WT. Characterization of TadA demonstrated that the protein is capable of binding heparin and of agglutinating purified lipid bodies. Finally, we observed that the TadA protein localizes to lipid bodies in R. opacus PD630 both in vivo and in vitro. Based on these data, we hypothesize that the TadA protein acts to aggregate small lipid bodies, found in cells during early stages of lipid storage, into larger lipid bodies and thus plays a key role in lipid body maturation in R. opacus PD630.While the majority of eubacteria (24, 33), and indeed many archaea (22, 33), store carbon as polyhydroxyalkanoate (PHA), a small subset of organisms, primarily actinomycetes, are capable of storing carbon in the form of triacylglycerol (TAG). TAG biosynthesis and storage has been observed in members of the genera Mycobacterium, Rhodococcus, Streptomyces, Nocardia, and others (4,6,11,12,19,20,36). Of these organisms, TAG biosynthesis and storage has been most extensively studied for the Gram-positive, non-spore-forming actinomycete Rhodococcus opacus, strain PD630 (1-6, 11, 12, 19, 20, 25, 36, 38-41).Several studies have demonstrated that R. opacus PD630 is capable of accumulating up to 76% of its cell dry weight (CDW) as TAG (summarized in reference 3). As is the case for PHA biosynthesis, TAG accumulation occurs during nitrogen starvation when carbon is in excess (1-3, 27, 41). Paralleling PHA biosynthesis further, TAG is stored in R. opacus PD630 in distinct inclusion bodies, termed lipid bodies (2,3,25,38,40). While several studies have sought to identify the underlying molecular and biochemical mechanisms behind TAG biosynthesis and storage in the form of lipid bodies, very little is known concerning these processes.We sought to identify genes and their products that are essential for lipid metabolism in R. opacus PD630. Utilizing a forward genetic approach, we identifie...

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“…For infectious bacteria, surface proteins are essential components of many aspects of pathogenesis (47,48). Host specificity, adhesion, invasion, molecular transport, and antimicrobial resistance are processes known to be directly mediated by proteins present at the surface interface (16,17,50,81). These proteins are also the primary target of the host immune system.…”

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confidence: 99%

Surface Proteome of “Mycobacterium avium subsp. hominissuis” during the Early Stages of Macrophage Infection

et al. 2012

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ABSTRACT“Mycobacterium aviumsubsp.hominissuis” is a robust and pervasive environmental bacterium that can cause opportunistic infections in humans. The bacterium overcomes the host immune response and is capable of surviving and replicating within host macrophages. Little is known about the bacterial mechanisms that facilitate these processes, but it can be expected that surface-exposed proteins play an important role. In this study, the selective biotinylation of surface-exposed proteins, streptavidin affinity purification, and shotgun mass spectrometry were used to characterize the surface-exposed proteome ofM. aviumsubsp.hominissuis. This analysis detected more than 100 proteins exposed at the bacterial surface ofM. aviumsubsp.hominissuis. Comparisons of surface-exposed proteins between conditions simulating early infection identified several groups of proteins whose presence on the bacterial surface was either constitutive or appeared to be unique to specific culture conditions. This proteomic profile facilitates an improved understanding ofM. aviumsubsp.hominissuisand how it establishes infection. Additionally, surface-exposed proteins are excellent targets for the host adaptive immune system, and their identification can inform the development of novel treatments, diagnostic tools, and vaccines for mycobacterial disease.

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Heparin-binding hemagglutinin (HBHA) ofMycobacterium lepraeis expressed during infection and enhances bacterial adherence to epithelial cells

Cited by 28 publications

References 25 publications

Interaction of Mycobacterium leprae with Human Airway Epithelial Cells: Adherence, Entry, Survival, and Identification of Potential Adhesins by Surface Proteome Analysis

Interaction of Mycobacterium leprae with Human Airway Epithelial Cells: Adherence, Entry, Survival, and Identification of Potential Adhesins by Surface Proteome Analysis

The Rhodococcus opacus PD630 Heparin-Binding Hemagglutinin Homolog TadA Mediates Lipid Body Formation

Surface Proteome of “Mycobacterium avium subsp. hominissuis” during the Early Stages of Macrophage Infection

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