Abstract:A mariner transposon bank was used to identify loci that contribute to the innate resistance of Listeria monocytogenes to the lantibiotic nisin. In addition to highlighting the importance of a number of loci previously associated with nisin resistance (mprF, virRS, and telA), a nisin-sensitive phenotype was associated with the disruption of anrB (lmo2115), a gene encoding the permease component of an ABC transporter. The contribution of anrB to nisin resistance was confirmed by the creation of nonpolar deletio… Show more
“…With respect to genes known to contribute to innate nisin resistance, it is notable that dltA, mprF, and anrB have been shown to be regulated by VirRS in L. monocytogenes (134,135). This strongly suggests that a significant role of the VirR/VirS system is to regulate resistance of L. monocytogenes to cationic peptides.…”
Section: Other Two-component Systemsmentioning
confidence: 89%
“…The permease component of the transporter was discovered as a result of screening of a mariner transposon bank of L. monocytogenes EGD-e mutants for nisin sensitivity and was found to be a BceAB-like transporter. Examination of a subsequently generated ⌬anrB deletion mutant also revealed associated increased sensitivities to the lantibiotic gallidermin, to bacitracin, and to a large number of -lactam antibiotics (134). Based on these results, it was proposed that AnrAB is a multidrug resistance (MDR) transporter that contributes to the innate antimicrobial resistance of L. monocytogenes.…”
SUMMARY
The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry.
“…With respect to genes known to contribute to innate nisin resistance, it is notable that dltA, mprF, and anrB have been shown to be regulated by VirRS in L. monocytogenes (134,135). This strongly suggests that a significant role of the VirR/VirS system is to regulate resistance of L. monocytogenes to cationic peptides.…”
Section: Other Two-component Systemsmentioning
confidence: 89%
“…The permease component of the transporter was discovered as a result of screening of a mariner transposon bank of L. monocytogenes EGD-e mutants for nisin sensitivity and was found to be a BceAB-like transporter. Examination of a subsequently generated ⌬anrB deletion mutant also revealed associated increased sensitivities to the lantibiotic gallidermin, to bacitracin, and to a large number of -lactam antibiotics (134). Based on these results, it was proposed that AnrAB is a multidrug resistance (MDR) transporter that contributes to the innate antimicrobial resistance of L. monocytogenes.…”
SUMMARY
The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry.
“…These immunity genes, which are probably remnants of bacteriocin gene clusters, may render the strains resistant to some bacteriocins if they are properly expressed. The presence of transporters that pump peptides out from the cell envelope may also be involved in bacteriocin resistance, in a similar manner as has been shown for lantibiotics (Collins et al, 2010;McBride & Sonenshein, 2011). Finally, it is also reasonable to believe that non-specific extracellular proteases that degrade the peptides can confer bacteriocin resistance.…”
Section: Transport Systems Confer Immunitymentioning
Due to their very potent antimicrobial activity against diverse food-spoiling bacteria and pathogens and their favourable biochemical properties, peptide bacteriocins from Gram-positive bacteria have long been considered promising for applications in food preservation or medical treatment. To take advantage of bacteriocins in different applications, it is crucial to have detailed knowledge on the molecular mechanisms by which these peptides recognize and kill target cells, how producer cells protect themselves from their own bacteriocin (self-immunity) and how target cells may develop resistance. In this review we discuss some important recent progress in these areas for the non-lantibiotic (class II) bacteriocins. We also discuss some examples of how the current wealth of genome sequences provides an invaluable source in the search for novel class II bacteriocins.
“…Additionally, producer self-resistance against lantibiotics is often mediated by ATP-binding cassette (ABC) transporters, collectively termed LanFEG, consisting of two membrane-spanning subunits and one ATPase, which are encoded in the biosynthetic loci for the respective lantibiotic and whose expression is regulated by a two-component system (TCS) of the same genetic locus (21). Over the last decade, several ABC transporters of a different type have been identified as resistance determinants against peptide antibiotics in nonproducing strains (5,12,32,35,39,41,44,51). The permeases of these transporters share unique domain architecture with 10 transmembrane helices and a large extracellular domain (ECD) of about 200 amino acids between helices 7 and 8.…”
In Firmicutes bacteria, ATP-binding cassette (ABC) transporters have been recognized as important resistance determinants against antimicrobial peptides. Together with neighboring two-component systems (TCSs), which regulate their expression, they form specific detoxification modules. Both the transport permease and sensor kinase components show unusual domain architecture: the permeases contain a large extracellular domain, while the sensor kinases lack an obvious input domain. One of the best-characterized examples is the bacitracin resistance module BceRS-BceAB of Bacillus subtilis. Strikingly, in this system, the ABC transporter and TCS have an absolute mutual requirement for each other in both sensing of and resistance to bacitracin, suggesting a novel mode of signal transduction in which the transporter constitutes the actual sensor. We identified over 250 such BceAB-like ABC transporters in the current databases. They occurred almost exclusively in Firmicutes bacteria, and 80% of the transporters were associated with a BceRS-like TCS. Phylogenetic analyses of the permease and sensor kinase components revealed a tight evolutionary correlation. Our findings suggest a direct regulatory interaction between the ABC transporters and TCSs, mediating communication between both components. Based on their observed coclustering and conservation of response regulator binding sites, we could identify putative corresponding two-component systems for transporters lacking a regulatory system in their immediate neighborhood. Taken together, our results show that these types of ABC transporters and TCSs have coevolved to form self-sufficient detoxification modules against antimicrobial peptides, widely distributed among Firmicutes bacteria.
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