2011
DOI: 10.1128/jb.05175-11
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Coevolution of ABC Transporters and Two-Component Regulatory Systems as Resistance Modules against Antimicrobial Peptides in Firmicutes Bacteria

Abstract: 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 e… Show more

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Cited by 138 publications
(197 citation statements)
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“…These accessory proteins are commonly membrane associated, which allows for ideal spatial locations to signal a two-component system. Classic examples of these membrane-associated proteins are ATP-binding cassette (ABC) transporters that facilitate the extrusion of antibiotics and the activation of adjacent two-component systems in S. aureus (GraRS), Streptococcus mutans (BceRS), and Bacillus subtilis (BceRS) (37)(38)(39). One of the most well characterized of these systems is BceRS in B. subtilis, in which the BceAB ABC transporter is essential for detection of bacitracin and the resulting activation of the cognate BceRS, which underscores the importance of these accessory proteins in two-component system regulation (40).…”
Section: Discussionmentioning
confidence: 99%
“…These accessory proteins are commonly membrane associated, which allows for ideal spatial locations to signal a two-component system. Classic examples of these membrane-associated proteins are ATP-binding cassette (ABC) transporters that facilitate the extrusion of antibiotics and the activation of adjacent two-component systems in S. aureus (GraRS), Streptococcus mutans (BceRS), and Bacillus subtilis (BceRS) (37)(38)(39). One of the most well characterized of these systems is BceRS in B. subtilis, in which the BceAB ABC transporter is essential for detection of bacitracin and the resulting activation of the cognate BceRS, which underscores the importance of these accessory proteins in two-component system regulation (40).…”
Section: Discussionmentioning
confidence: 99%
“…It appears that the presence of antimicrobial peptides cannot be detected by these histidine kinases alone but rather that this resistance module relies on the transporters for stimulus recognition, i.e., in the presence of an antimicrobial peptide, the transporter somehow communicates with the sensor kinase. It is believed that this involves direct contact between the transporter and the histidine kinase (105,107). However, the mechanism by which signaling occurs is as yet unknown.…”
Section: Bcers-like Two-component Systemsmentioning
confidence: 99%
“…Furthermore, although signaling and resistance are functionally interconnected, several identified mutations had stronger effects over one than the other (118). The cooccurrence and coevolution of Pep7E transporters and the BceRS-like TCS led to the hypothesis that a functional link always exists between these systems, in which they cooperate in both signaling and detoxification (105). The exact means by which BceAB detoxification occurs has not been fully elucidated.…”
Section: Bcers-like Two-component Systemsmentioning
confidence: 99%
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