Lysozyme Secretion by Submucosal Glands Protects the Airway from Bacterial Infection

Dajani, Rana; Zhang, Yulong; Taft, Peter J.; Travis, Sue M.; Starner, Timothy D.; Olsen, Ansgar S.; Zabner, Joseph; Welsh, Michael J.; Engelhardt, John F.

doi:10.1165/rcmb.2005-0059oc

Cited by 102 publications

(98 citation statements)

References 24 publications

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“…Because lysozyme is produced abundantly in epithelial secretions and lysosomal compartments of phagocytic cells (17,50), the cell surface association and lysozyme binding properties of LprI may be crucial for maintaining the structural integrity of M. tuberculosis during intracellular infection. Lysozyme resistance may be especially important for pathogenic mycobacteria as they need to protect the thick peptidoglycan layer of their cell wall from the hydrolyzing activities of lysozyme produced by their host during microbial infection.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, to understand the physiological function of LprI, we utilized M. smegmatis as an alternative model primarily due to the fact that it lacks lprI gene and that it has been used as an alternative host to understand the function(s) of several M. tuberculosis proteins (47,48). Because high concentrations of lysozyme are secreted as a part of the host defense system in various organs including mucosal surfaces and macrophages (49,50) and recombinant LprI effectively relieved the toxicity of lysozyme in vitro, we checked the implications of LprI during intracellular infection of primary cell lines, viz. MDMs and peritoneal macrophages (Fig.…”

Section: Lpri Is a Novel Lipoprotein Of M Tuberculosis Complex-mentioning

confidence: 99%

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Lipoprotein LprI of Mycobacterium tuberculosis Acts as a Lysozyme Inhibitor

Sethi¹,

Mahajan²,

Singh

et al. 2016

Journal of Biological Chemistry

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Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most dreaded human pathogens that affect millions of lives worldwide (1). The inexplicable success of M. tuberculosis as a human pathogen relies on its ability to utilize a number of defense strategies to adapt its metabolism in response to a plethora of environmental challenges during the course of its pathogenic cycle (2, 3). Several of the components of its protein machinery have emerged as virulence factors with vital implications. Among these, lipoproteins play pivotal roles in several functions related to its virulence and host-pathogen interactions (4 -6). Genome analysis of mycobacteria indicated that the number of lipoproteins is much higher in the pathogenic mycobacteria in comparison with their non-pathogenic counterparts, and M. tuberculosis houses the highest number of lipoproteins.LprI is a novel lipoprotein that is exclusively present in pathogenic mycobacteria belonging to M. tuberculosis complex. The genomic location of the lprI gene is conserved among pathogenic mycobacteria where it has been identified as an operon partner of the glbN gene, which encodes truncated hemoglobin (HbN) 3 (7,8). The lprI gene is positioned adjacent to the glbN gene, separated through an intergenic distance of 58 nucleotides, and their co-transcription has been observed in Mycobacterium bovis (9), indicating that these two proteins may have functional correlation. The HbN of M. tuberculosis carries potent nitric oxide (NO) detoxification ability (8 -10) and is post-translationally modified by a glycan linkage that facilitates adherence and phagocytosis of cells during macrophage infection (11). The functional relevance of the co-occurrence of LprI with HbN in M. tuberculosis is unknown. Similar co-existence of a lipoprotein, LprG, along with Rv1410, which encodes a small molecule transporter, P55 (an operon conserved in M. tuberculosis complex), has also been observed in M. tuberculosis (12) where they function in a cooperative and synchronized manner. Because the HbN of M. tuberculosis plays a vital role in and is also involved in modulating host-pathogen interactions during intracellular infection of M. tuberculosis, it is likely that the glbN-lprI operon may also have some significant implications in the physiology of tubercle bacillus. LprI is an uncharacterized lipoprotein of M. tuberculosis complex; therefore, in the absence of any knowledge on LprI, its physiological function and implications of its co-existence with the HbN in M. tuberculosis are difficult to understand. To investigate the crucial implications of HbN in modulating the host-pathogen interactions and immune system of the host by providing aid in the better survival and sustenance of M. tuberculosis during intracellular infection, it is important to study the functionality of the LprI to understand functional implications of their co-occurrence in M. tuberculosis.In silico analysis unraveled that LprI carries a lysozyme-binding motif of the membrane-bound lysozyme in...

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Section: Discussionmentioning

confidence: 99%

Section: Lpri Is a Novel Lipoprotein Of M Tuberculosis Complex-mentioning

confidence: 99%

Lipoprotein LprI of Mycobacterium tuberculosis Acts as a Lysozyme Inhibitor

Sethi¹,

Mahajan²,

Singh

et al. 2016

Journal of Biological Chemistry

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“…Thus, to detect LPO activity requires replenishing secretions with the estimated low physiological [H 2 O 2 ] something not generally added in studies of antibacterial activity in airway secretions (e.g. [50]). These levels of H 2 O 2 , added to in vitro peroxidase antibacterial systems, are well below the levels needed for killing of bacteria by H 2 O 2 alone (e.g.…”

Section: Discussionmentioning

confidence: 99%

The lactoperoxidase system links anion transport to host defense in cystic fibrosis

et al. 2006

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“…Many of these glandular secretory products, such as lysozyme and lactoperoxidase, are critical to maintaining sterility of the proximal airway (15,16). Furthermore, ex vivo models of airways with and without SMGs suggest that the presence of SMGs significantly influences bioelectric and fluid transport properties of the airway (13,17).…”

Section: Smgs In the Airwaymentioning

confidence: 99%

The Glandular Stem/Progenitor Cell Niche in Airway Development and Repair

Liu¹,

Engelhardt²

2008

Proceedings of the American Thoracic Society

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Airway submucosal glands (SMGs) are major secretory structures that lie beneath the epithelium of the cartilaginous airway. These glands are believed to play important roles in normal lung function and airway innate immunity by secreting antibacterial factors, mucus, and fluid into the airway lumen. Recent studies have suggested that SMGs may additionally serve as a protective niche for adult epithelial stem/progenitor cells of the proximal airways. As in the case of other adult stem cell niches, SMGs are believed to provide the localized environmental signals required to both maintain and mobilize stem/progenitor cells, in the setting of normal cellular turnover or injury. Aberrant proliferation and differentiation of glandular stem/progenitor cells may be associated with several hypersecretory lung diseases, including chronic bronchitis, asthma, and cystic fibrosis. To better understand the molecular mechanisms that regulate the specification and proliferation of glandular stem/ progenitor cells in lung diseases associated with SMG hypertrophy and hyperplasia, researchers have begun to search for the molecular signals and cell types responsible for establishing the glandular stem/progenitor cell niche, and to dissect how these determinants of the niche change in the setting of proximal airway injury and repair. Such studies have revealed certain similarities between stem/ progenitor cell niches of the distal conducting airways and the SMGs of the proximal airways.

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Lysozyme Secretion by Submucosal Glands Protects the Airway from Bacterial Infection

Cited by 102 publications

References 24 publications

Lipoprotein LprI of Mycobacterium tuberculosis Acts as a Lysozyme Inhibitor

Lipoprotein LprI of Mycobacterium tuberculosis Acts as a Lysozyme Inhibitor

The lactoperoxidase system links anion transport to host defense in cystic fibrosis

The Glandular Stem/Progenitor Cell Niche in Airway Development and Repair

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