Mechanism of antimicrobial peptide resistance mediated by an ABC transporter coupled to a two-component regulatory system in Streptococcus pneumoniae – SpABC-TCS

Antibiotic resistance is an increasing global public health threat that concerns all major bacterial pathogens and therapeutic drugs. Antimicrobial peptides are an important component of the first line of defense of most living organisms against invading bacteria and are considered as promising alternative therapeutics to fight pathogens. However, bacteria have also evolved mechanisms to resist antimicrobial peptides, one of the most prominent being the use of dedicated ABC (“ATP-Binding Cassette”) transporters. A unique property of these transporters is that they cooperate with two-component regulatory systems to sense the presence of antimicrobial peptides and, in turn, activate the expression of the transporter genes thereby increasing the levels of cellular resistance. The functioning of these unique sensor/transport systems is, however, poorly understood and we propose here to elucidate the molecular mechanism that governs such a resistant module in Streptococcus pneumoniae, a deadly human pathogen.