The @entity794 two-component regulatory system, GraRS, is involved in resistance to killing by distinct @entity2132 ( @entity2132 ). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the @entity794 surface charge. However, the detailed mechanism(s) by which the @entity3793 kinase, GraS, senses specific @entity2132 is not well defined. Here, we studied a well-characterized clinical @entity3256 -resistant @entity794 ( @entity794 (MW2), its isogenic graS deletion mutant (  graS strain), a nonameric extracellular loop mutant (  EL strain), and four residue-specific   EL mutants ( @entity68158 , @entity68159 , @entity68160 , and @entity68161 strains). The   graS and   EL strains were unable to induce mprF and dltA expression and, in turn, demonstrated significantly increased susceptibilities to @entity13757 , @entity6414 , and two prototypical @entity2132 ( @entity11915 and RP-1). Further, @entity68159 , @entity68160 , and @entity68162 - @entity68163 - @entity68164   EL mutations correlated with moderate @entity2033 susceptibility. Reductions of mprF and dltA induction by PMB were also found in the   EL mutants, suggesting these residues are pivotal to appropriate activation of the GraS sensor kinase. Importantly, a synthetic exogenous soluble EL mimic of GraS protected the parental MW2 strain against @entity11915 - and RP-1-mediated killing, suggesting a direct interaction of the EL with @entity2132 in GraS activation. In vivo, the   graS and   EL strains displayed @entity353 in achieved target tissue @entity794 counts in an @entity884 model. Taken together, our results provide new insights into potential roles of GraS in @entity794 sensing of @entity2132 to induce adaptive survival responses to these molecules.

Site-specific mutation of the sensor kinase GraS in XXXX alters the adaptive response to distinct cationic antimicrobial peptides.

@entity3256 :: ('MESH:D008712', 'Chemical') :: ['methicillin'] @entity68164 :: ('p|SUB|D|41|G', 'ProteinMutation') :: ['D41G'] @entity353 :: ('MESH:D015431', 'Disease') :: ['dramatic reductions'] @entity68161 :: ('|SUB|D,GD,GD|35,37,41|G', 'ProteinMutation') :: ['D35G D37G D41G'] @entity3793 :: ('CHEBI:27570', 'Chemical') :: ['histidine'] @entity6414 :: ('MESH:D011112', 'Chemical') :: ['polymyxin B'] @entity794 :: ('1280', 'Species') :: ['MRSA) strain', 'Staphylococcus aureus', 'MRSA', 'S. aureus'] @entity11915 :: ('4884', 'Gene') :: ['hNP-1'] @entity68162 :: ('p|SUB|D|35|G', 'ProteinMutation') :: ['D35G'] @entity68160 :: ('p|SUB|P|39|S', 'ProteinMutation') :: ['P39S'] @entity68163 :: ('p|SUB|D|37|G', 'ProteinMutation') :: ['D37G'] @entity2033 :: ('MESH:D006816', 'Disease') :: ['increases in HD-CAP'] @entity68158 :: ('p|SUB|D|37|A', 'ProteinMutation') :: ['D37A'] @entity2132 :: ('MESH:D006086', 'Disease') :: ['host defense cationic antimicrobial peptides', 'HD-CAPs'] @entity68159 :: ('p|SUB|P|39|A', 'ProteinMutation') :: ['P39A'] @entity13757 :: ('MESH:D017576', 'Chemical') :: ['daptomycin'] @entity884 :: ('MESH:D004696', 'Disease') :: ['endocarditis']
@entity794 :: (1280,Species) :: ['Staphylococcus aureus']
