Heavy Metal Toxicity in Armed Conflicts Potentiates AMR in A. baumannii by Selecting for Antibiotic and Heavy Metal Co-resistance Mechanisms

Abstract

Acinetobacter baumannii has become increasingly resistant to leading antimicrobial agents since the 1970s. Increased resistance appears linked to armed conflicts, notably since widespread media stories amplified clinical reports in the wake of the American invasion of Iraq in 2003. Antimicrobial resistance is usually assumed to arise through selection pressure exerted by antimicrobial treatment, particularly where treatment is inadequate, as in the case of low dosing, substandard antimicrobial agents, or shortened treatment course. Recently attention has focused on an emerging pathogen, multi-drug resistant A. baumannii (MDRAb). MDRAb gained media attention after being identified in American soldiers returning from Iraq and treated in US military facilities, where it was termed "Iraqibacter." However, MDRAb is strongly associated in the literature with war injuries that are heavily contaminated by both environmental debris and shrapnel from weapons. Both may harbor substantial amounts of toxic heavy metals. Interestingly, heavy metals are known to also select for antimicrobial resistance. In this review we highlight the potential causes of antimicrobial resistance by heavy metals, with a focus on its emergence in A. baumanni in war zones.

Emerging Concern for Silver Nanoparticle Resistance in Acinetobacter baumannii and Other Bacteria

“…Destroyed infrastructure and metal-based military equipment (i.e., munitions, ordnance, and explosives) are known to contaminate environments through heavy metal leaching (Gębka et al, 2016;Vänskä et al, 2019). It has been proposed that metal exposure on A. baumannii in contaminated soil or water, for example, could have promoted the co-selection of antibiotic resistance, which resulted in the increased prevalence of MDR-resistant A. baumannii infections in soldiers exposed to these environments during combat (Bazzi et al, 2020).…”

Mechanisms Protecting Acinetobacter baumannii against Multiple Stresses Triggered by the Host Immune Response, Antibiotics and Outside-Host Environment

“…Another mechanism involved in bacterial resistance is called co-regulatory resistance. This occurs when resistant genes to antimicrobial agents are controlled by regulatory proteins [ 218 ]. Commonality of target sites between different class of antibiotics leads to the selection of mutants and the emergence of cross-resistance, as well as the co-selection and persistence of antibiotic-resistant strains.…”

AMR and Covid-19 on the Frontline: A Call to Rethink War, WASH, and Public Health

“…Responses which have been developed to deal with covid-19 can learn a lot from our stumbling in the dark with AMR from Aleppo to Tripoli, through Gaza and Aden. Here, resistant bacteria can come in on a sniper’s bullet [ 3 ], mutate via surgical instruments that are disinfected in contaminated water [ 4 ], and be carried back to the community through the hospital’s wastewater pipes [ 5 ].…”