TY - JOUR
T1 - Biofilms of Mycobacterium abscessus complex can be sensitized to antibiotics by disaggregation and oxygenation
AU - Kolpen, Mette
AU - Jensen, Peter Østrup
AU - Qvist, Tavs
AU - Kragh, Kasper Nørskov
AU - Ravnholt, Cecillie
AU - Fritz, Blaine Gabriel
AU - Johansen, Ulla Rydahl
AU - Bjarnsholt, Thomas
AU - Høiby, Niels
N1 - Copyright © 2020 American Society for Microbiology.
PY - 2020/1/27
Y1 - 2020/1/27
N2 - Pulmonary infection with the multidrug-resistant
Mycobacterium abscessus complex (MABSC) is difficult to treat in individuals with cystic fibrosis (CF). MABSC grows as biofilm aggregates in CF patient lungs, which are known to have anaerobic niches. How aggregation and anoxic conditions affect antibiotic tolerance is not well understood. We sought to determine whether disaggregation and oxygen availability sensitize MABSC isolates to recommended antibiotics. We tested the susceptibilities of 33 isolates from 22 CF patients with MABSC infection and a reference strain to the following antibiotics: amikacin, azithromycin, cefoxitin, ciprofloxacin, clarithromycin, imipenem, kanamycin, linezolid, moxifloxacin, rifampin, tigecycline, and sulfamethoxazole-trimethoprim. Isolates were grown in Mueller-Hinton broth with and without the disaggregating detergent Tween 80 (5%). Time-kill curves at days 1 and 3 were generated for oxic and anoxic amikacin treatment in 4-fold dilutions ranging from 2 to 512 mg liter
-1 Scanning electron microscopy was used to visualize the aggregation patterns, while confocal laser scanning microscopy and microrespirometry were used to visualize biofilm growth patterns. Disruption of MABSC aggregates increased susceptibility to amikacin, tigecycline, kanamycin, azithromycin, imipenem, cefoxitin, and clarithromycin (
P < 0.05,
n = 29 to 31). Oxygenation enhanced the killing of disaggregated MABSC isolates by amikacin (
P < 0.05) by 1 to 6 log units when 2 to 512 mg liter
-1 of amikacin was used. This study explains why current drug susceptibility testing results correlate poorly with treatment outcomes. The conditions achieved by oxic culturing of planktonic isolates
in vitro do not resemble the hypoxic conditions in CF patient lungs. Biofilm disruption and increased O
2 availability during antibiotic therapy may be new therapeutic strategies for chronic MABSC infection.
AB - Pulmonary infection with the multidrug-resistant
Mycobacterium abscessus complex (MABSC) is difficult to treat in individuals with cystic fibrosis (CF). MABSC grows as biofilm aggregates in CF patient lungs, which are known to have anaerobic niches. How aggregation and anoxic conditions affect antibiotic tolerance is not well understood. We sought to determine whether disaggregation and oxygen availability sensitize MABSC isolates to recommended antibiotics. We tested the susceptibilities of 33 isolates from 22 CF patients with MABSC infection and a reference strain to the following antibiotics: amikacin, azithromycin, cefoxitin, ciprofloxacin, clarithromycin, imipenem, kanamycin, linezolid, moxifloxacin, rifampin, tigecycline, and sulfamethoxazole-trimethoprim. Isolates were grown in Mueller-Hinton broth with and without the disaggregating detergent Tween 80 (5%). Time-kill curves at days 1 and 3 were generated for oxic and anoxic amikacin treatment in 4-fold dilutions ranging from 2 to 512 mg liter
-1 Scanning electron microscopy was used to visualize the aggregation patterns, while confocal laser scanning microscopy and microrespirometry were used to visualize biofilm growth patterns. Disruption of MABSC aggregates increased susceptibility to amikacin, tigecycline, kanamycin, azithromycin, imipenem, cefoxitin, and clarithromycin (
P < 0.05,
n = 29 to 31). Oxygenation enhanced the killing of disaggregated MABSC isolates by amikacin (
P < 0.05) by 1 to 6 log units when 2 to 512 mg liter
-1 of amikacin was used. This study explains why current drug susceptibility testing results correlate poorly with treatment outcomes. The conditions achieved by oxic culturing of planktonic isolates
in vitro do not resemble the hypoxic conditions in CF patient lungs. Biofilm disruption and increased O
2 availability during antibiotic therapy may be new therapeutic strategies for chronic MABSC infection.
KW - Antimicrobial resistance
KW - Biofilm
KW - Cystic fibrosis
KW - Mycobacterium abscessus complex
KW - Oxygenation
KW - Aerobiosis
KW - Cystic Fibrosis/complications
KW - Biofilms/drug effects
KW - Humans
KW - Oxygen/pharmacology
KW - Male
KW - Anti-Bacterial Agents/pharmacology
KW - Microbial Sensitivity Tests
KW - Young Adult
KW - Polysorbates/pharmacology
KW - Drug Resistance, Multiple, Bacterial
KW - Mycobacterium Infections, Nontuberculous/drug therapy
KW - Adolescent
KW - Female
KW - Lung/microbiology
KW - Child
KW - Surface-Active Agents/pharmacology
KW - Mycobacterium abscessus/drug effects
KW - oxygenation
KW - antimicrobial resistance
KW - cystic fibrosis
KW - biofilm
U2 - 10.1128/AAC.01212-19
DO - 10.1128/AAC.01212-19
M3 - Journal article
C2 - 31740557
VL - 64
SP - e01212-19
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 2
ER -