A bacterial sensory system that activates resistance to innate immune defenses: potential targets for antimicrobial therapeutics.
Bacteria posses multiple two component regulatory systems consisting typically of a kinase and a transcription factor that, in concert, monitor the concentrations of particular extracellular factors and regulate specific gene expression accordingly. Salmonella possess PhoP-PhoQ, which are activated under conditions of suboptimal [Mg(2+)] and result in gene expression leading to greater stability of the outer membrane. New research identifies PhoQ as a receptor for sublethal concentrations of antimicrobial peptides (AMPs), adapting bacteria for survival. The development of AMPs that do not activate Phop-PhoQ, however, should proceed with great caution: AMPs are part of the host innate immune response and bacterial resistance to newly developed AMPs could possibly lead to intractable infection in immunocompetent hosts.
Brodsky
Igor E
IE
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.
Gunn
John S
JS
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D007113:Immunity, Innate; D008274:Magnesium / Q000502:physiology; D019779:Salmonella enterica / Q000502:physiology; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; D037521:Virulence Factors; C061064:PhoP protein, Bacteria; D008274:Magnesium