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Article

Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii

1
Department of Microbiology, Division of Basic Medical Science, National Organization for Drug Control and Research (NODCAR), 12553 Giza, Egypt
2
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Cairo, 11562 Cairo, Egypt
*
Author to whom correspondence should be addressed.
Academic Editor: Tim Downing
Received: 10 March 2020 / Revised: 1 April 2020 / Accepted: 2 April 2020 / Published: 6 April 2020
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
Acinetobacter baumannii is one of the most common causes of nosocomial infections in intensive care units. Its ability to acquire diverse mechanisms of resistance limits the therapeutic choices for its treatment. This especially concerns colistin, which has been reused recently as a last-resort drug against A. baumannii. Here, we explored the impact of gaining colistin resistance on the susceptibility of A. baumannii to other antibiotics and linked colistin resistance acquisition to a gene mutation in A. baumannii. The susceptibility of 95 A. baumannii isolates revealed that 89 isolates were multi-drug resistance (MDR), and nine isolates were resistant to colistin. Subsequently, three isolates, i.e., MS48, MS50, and MS64, exhibited different resistance patterns when colistin resistance was induced and gained resistance to almost all tested antibiotics. Upon TEM examination, morphological alterations were reported for all induced isolates and a colistin-resistant clinical isolate (MS34Col-R) compared to the parental sensitive strains. Finally, genetic alterations in PmrB and LpxACD were assessed, and a point mutation in LpxD was identified in the MS64Col-R and MS34Col-R mutants, corresponding to Lys117Glu substitution in the lipid-binding domain. Our findings shed light on the implications of using colistin in the treatment of A. baumannii, especially at sub-minimum inhibitory concentrations concentrations, since cross-resistance to other classes of antibiotics may emerge, beside the rapid acquisition of resistance against colistin itself due to distinct genetic events. View Full-Text
Keywords: Acinetobacter baumannii; colistin; cross-resistance; LpxD mutation; pmrB mutation Acinetobacter baumannii; colistin; cross-resistance; LpxD mutation; pmrB mutation
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MDPI and ACS Style

Saleh, N.M.; Hesham, M.S.; Amin, M.A.; Samir Mohamed, R. Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii. Antibiotics 2020, 9, 164. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9040164

AMA Style

Saleh NM, Hesham MS, Amin MA, Samir Mohamed R. Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii. Antibiotics. 2020; 9(4):164. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9040164

Chicago/Turabian Style

Saleh, Neveen M., Marwa S. Hesham, Magdy A. Amin, and Reham Samir Mohamed. 2020. "Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii" Antibiotics 9, no. 4: 164. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9040164

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