Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii

Autor: Michael J. Noto, William J. Burns, Christiaan D. Wijers, Eric P. Skaar, M. Indriati Hood-Pishchany, Kelli L. Boyd, Lauren D. Palmer, Ly Pham
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Acinetobacter baumannii
Pulmonology
Physiology
Neutrophils
medicine.disease_cause
Pathology and Laboratory Medicine
White Blood Cells
Mice
Antibiotics
Animal Cells
Kanamycin
Immune Physiology
Medicine and Health Sciences
Biology (General)
Lung
Mice
Knockout
0303 health sciences
Innate Immune System
Phagocytes
Antimicrobials
030302 biochemistry & molecular biology
Aminoglycoside
Drugs
3. Good health
Bacterial Pathogens
Medical Microbiology
Cytokines
Female
Pathogens
Cellular Types
Chemokines
Research Article
Acinetobacter Infections
QH301-705.5
Immune Cells
Immunology
Lung injury
Biology
Microbiology
03 medical and health sciences
Immune system
Immunity
Microbial Control
Virology
Genetics
medicine
Pneumonia
Bacterial
Animals
Molecular Biology
Lysogeny
Microbial Pathogens
030304 developmental biology
Pharmacology
Innate immune system
Blood Cells
Bacterial pneumonia
Biology and Life Sciences
Pathogenic bacteria
Pneumonia
Cell Biology
Molecular Development
biochemical phenomena
metabolism
and nutrition
RC581-607
medicine.disease
biology.organism_classification
Viral Replication
Immunity
Innate
Antibiotic Resistance
Immune System
bacteria
Parasitology
Antimicrobial Resistance
Immunologic diseases. Allergy
Developmental Biology
Zdroj: PLoS Pathogens, Vol 16, Iss 3, p e1008374 (2020)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibiotic results in alterations to the bacterium that interact with lung innate immunity resulting in enhanced bacterial clearance. Co-inoculation of mice with A. baumannii grown in the presence and absence of the aminoglycoside, kanamycin, induces enhanced clearance of a non-kanamycin-propagated strain. This finding can be replicated when kanamycin-propagated A. baumannii is killed prior to co-inoculation of mice, indicating the enhanced bacterial clearance results from interactions with innate host defenses in the lung. Infection with kanamycin-propagated A. baumannii alters the kinetics of phagocyte recruitment to the lung and reduces pro- and anti-inflammatory cytokine and chemokine production in the lung and blood. This culminates in reduced histopathologic evidence of lung injury during infection despite enhanced bacterial clearance. Further, the antibacterial response induced by killed aminoglycoside-propagated A. baumannii enhances the clearance of multiple clinically relevant Gram-negative pathogens from the lungs of infected mice. Together, these findings exemplify cooperation between antibiotics and the host immune system that affords protection against multiple antibiotic-resistant bacterial pathogens. Further, these findings highlight the potential for the development of a broad-spectrum therapeutic that exploits a similar mechanism to that described here and acts as an innate immunity modulator.
Author summary Preserving the ability to treat infectious diseases with antibiotics in the face of the rapid proliferation of drug-resistant bacterial pathogens is among the greatest challenges facing medicine. Efforts to combat antimicrobial resistance may include strategies to maximize the utility of existing antibiotics while also identifying new therapeutic targets to treat bacterial infections. Acinetobacter baumannii is a human pathogen and strains of A. baumannii have acquired multi- and pan-antibiotic resistance. Here, we demonstrate that A. baumannii that is resistant to the aminoglycoside class of antibiotics is rapidly cleared from the lungs of mice when exposed to aminoglycoside antibiotics. Exposure to aminoglycosides induces changes in A. baumannii that interact with mouse antibacterial defenses, leading to rapid clearance of the infection. Further, killed aminoglycoside-exposed A. baumannii interacts with innate immunity in the lung to enhance the clearance of other pathogenic bacteria. These findings indicate that pneumonia caused by aminoglycoside-resistant A. baumannii may be effectively treated with aminoglycoside antibiotics and also suggests that the host immune response can be targeted to enhance the clearance of bacterial infections.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje