2017
DOI: 10.1002/1873-3468.12848
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Dissecting the structure–function relationship in lysozyme domain of mycobacteriophage D29‐encoded peptidoglycan hydrolase

Abstract: Most bacteriophages rapidly infect and kill bacteria and, therefore, qualify as the next generation therapeutics for rapidly emerging drug-resistant bacteria such as Mycobacterium tuberculosis. We have previously characterized the mycobacteriophage D29-generated endolysin, Lysin A, for its activity against mycobacteria. Here, we present a detailed characterization of the lysozyme domain (LD) of D29 Lysin A that hydrolyzes peptidoglycan of both gram-positive and gram-negative bacteria with high potency. By char… Show more

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Cited by 13 publications
(7 citation statements)
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“…In addition, 71.7% of the prophages have genes encoding lysozymes and 54.7% have genes encoding holins. Lysozymes are peptidoglycan hydrolases and holins cause plasmatic membrane damage, the action of these enzymes leading to cell disruption 11 , 32 . The presence of these enzymes characterizes these phages as infective, highlighting an attractive feature for their isolation by induction and infection assays with different strains, as seen by Walker et al .…”
Section: Discussionmentioning
confidence: 99%
“…In addition, 71.7% of the prophages have genes encoding lysozymes and 54.7% have genes encoding holins. Lysozymes are peptidoglycan hydrolases and holins cause plasmatic membrane damage, the action of these enzymes leading to cell disruption 11 , 32 . The presence of these enzymes characterizes these phages as infective, highlighting an attractive feature for their isolation by induction and infection assays with different strains, as seen by Walker et al .…”
Section: Discussionmentioning
confidence: 99%
“…The ability of mycobacteriophage D29 to quickly penetrate and eradicate pathogens is the reason why researchers have considered it as a new therapeutic option against MDR and XDR bacteria, especially Mtb 53. This mycobacteriophage is used for several targets, particularly in TB diagnosis and probably in TB treatment 54.…”
Section: Phage Therapy In Tuberculosismentioning
confidence: 99%
“…Lysin A coded by gp10 hydrolyzes peptidoglycan of bacterial cell walls 57. Gp12 encodes Lysin B that leads to the dissemination of mycolic acid from the peptidoglycans in mycobacterial cell wall 53,58. Holin as a membrane pore-forming protein participates in the transfer of lysins from the cytosol to the periplasm 59.…”
Section: Phage Therapy In Tuberculosismentioning
confidence: 99%
“…In another study, the same authors proposed that the D29 LysA interdomain interaction occurs intramolecularly and is facilitated by a charged linker that connects the two domains [ 27 ]. In addition, the central catalytic domain that has been predicted to possess glycoside hydrolase (GH19) activity was shown to possess a residue R198, positioned away from the catalytic site and not directly involved in substrate binding, which plays a critical role in the maintenance of the substrate-binding cavity [ 76 ]. Taken together these data indicate that mycobacteriophage endolysin activity regulation may be more complex than previously anticipated, involving intramolecular domains interaction and synthesis of secondary gene products in order to optimize mycobacteria CW binding and enzyme activation; these mechanisms may improve PG breakdown which will culminate in optimal bacterial cell rupture and phage release.…”
Section: Mycobacteriophages Endolysin (Lysa)—the Essential Lysis Pmentioning
confidence: 99%