title: Resistance to Acute Macrophage Killing Promotes Airway Fitness of Prevalent Community-Acquired Staphylococcus aureus Strains.
abstract: The incidence of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in otherwise healthy individuals is increasing. To investigate the mechanism underlying the epidemiological success of predominant community-associated (CA)-MRSA strains, we examined their fitness traits during the initial interaction between bacteria and the host occurring in the lower airway. Using a mouse respiratory infection model, we show that clinical isolates often responsible for CA infections are highly resistant to clearance from healthy airways, whereas S. aureus strains not as prevalent or traditionally associated with hospital-associated infections are relatively susceptible. Mechanistically, the competitive fitness of S. aureus is a result of both agr-dependent and -independent resistance to innate bacterial killing. Furthermore, we show that rather than evasion from neutrophil-dependent bactericidal process, the observed S. aureus fitness in the lower airways is due to its intrinsic resistance to resident alveolar macrophage-mediated intracellular killing. Importantly, we demonstrate that the virulence determinants responsible for bacterial persistence in immune-competent mice are dispensable in mice with predisposing conditions such as influenza infection. Taken together, these novel findings of the improved competence of predominant CA-MRSA strains to survive innate killing in healthy hosts, particularly at the very beginning stage of infection, provide a unique insight into their epidemiological success.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Vijaya Kumar
authors.identifier: 0000-0001-6155-1138
authors.initials: VK
authors.lastname: Yajjala
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Vinai Chittezham
authors.identifier: 0000-0002-7886-0727
authors.initials: VC
authors.lastname: Thomas
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Scherr
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Fischer
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Fey
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Bayles
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 Keer.sun@unmc.edu.
authors.forename: Keer
authors.initials: K
authors.lastname: Sun
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002460:Cell Line; D060085:Coinfection / Q000276:immunology; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D053208:Kaplan-Meier Estimate; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology*; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology*; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D037521:Virulence Factors