title: On the in vivo significance of bacterial resistance to antimicrobial peptides.
abstract: Antimicrobial peptides (AMPs) are at the front-line of host defense during infection and play critical roles both in reducing the microbial load early during infection and in linking innate to adaptive immunity. However, successful pathogens have developed mechanisms to resist AMPs. Although considerable progress has been made in elucidating AMP-resistance mechanisms of pathogenic bacteria in vitro, less is known regarding the in vivo significance of such resistance. Nevertheless, progress has been made in this area, largely by using murine models and, in two instances, human models of infection. Herein, we review progress on the use of in vivo infection models in AMP research and discuss the AMP resistance mechanisms that have been established by in vivo studies to contribute to microbial infection. We posit that in vivo infection models are essential tools for investigators to understand the significance to pathogenesis of genetic changes that impact levels of bacterial susceptibility to AMPs. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, 635 Barnhill Drive MS-420, Indianapolis, IN 46254, USA. Electronic address: mebauer@iupui.edu.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Bauer
authors.affiliation: Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, GA 30033, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: wshafer@emory.edu.
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005838:Genotype; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D051379:Mice; D050296:Microbial Viability; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: Antimicrobial peptides; Cell envelope modifications; In vivo models; Pathogenesis; Resistance mechanisms; Transporters