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.

This study assesses the potential effect of micafungin, an antifungal agent known to inhibit 1,3-β-D-glucan synthesis in Candida albicans, on biofilm formation of selected Pseudomonas aeruginosa isolates by decreasing the synthesis of extracellular matrix β-D-glucan forming units. The effect of an optimal therapeutic dose of 10 mg ml(-1) micafungin on the production of biofilm was monitored in vitro using a microtiter plate assay. Phenotypic reduction in the formation of biofilm was significant (based on average optical density; p < 0.05) in most of the isolates. Moreover, the relative gene expression of biofilm encoding genes for alginate and pellicles (algC and pelC, respectively), and the cell wall 1,3-β-D-glucan encoding gene (ndvB) was evaluated using quantitative reverse transcription PCR. For all the genes tested, the levels of mRNA transcription were also decreased significantly (p < 0.05) in micafungin-treated samples cf. their untreated counterparts. In conclusion, this study presents micafungin as a potential agent for disrupting the structure of a biofilm of P. aeruginosa allowing the possible exposure and treatment of core-planktonic cells.

Micafungin inhibits biofilm formation by impeding 1,3-β-D-glucan synthesis in Candida albicans. Since Pseudomonas aeruginosa also has 1,3-β-D-glucan in its cell wall, this study assessed the effects of antibacterial agents in vitro and in vivo on micafungin-treated biofilm-forming P. aeruginosa isolates. After treatment with micafungin as well as with a panel of four antibacterial agents, biofilm production was significantly reduced as measured by spectrophotometry. The relative mRNA transcription levels for the genes encoding pellicles (pelC) and cell wall 1,3-β-D-glucan (ndvB), which were measured by quantitative reverse transcription PCR (qRT-PCR), significantly decreased with micafungin treatment. In vivo, the survival rates of P. aeruginosa-infected BALB/c mice significantly increased after combined treatment with micafungin and each of the antibacterial agents. Of these treatments, the combination of micafungin with levofloxacin had the highest survival rate; this combination was the most effective treatment against P. aeruginosa-induced infection.

Editorial on the Research Topic Combating Antimicrobial Resistance-A One Health Approach Antimicrobial resistance (AMR) is a life threatening and a very serious global health problem. There is an increasing alarming concern regarding the emergence of multi-drug resistant (MDR) superbugs. Infections emerging from such pathogens are in most cases unresponsive to treatment with few, if any, antimicrobial agents currently available and effective. This issue is causing the development of two eras, a pre-antimicrobial agent era and raises concerns regarding a post-antimicrobial agent era, where the last resort antimicrobial agents are not potent to treat infections caused by Gram-positive and Gram-negative MDR strains. Given the complexity of the AMR challenge at the level of human and animal health, in addition to the impact on the environment, it seems very important to stress and emphasize the role of a "One Health" approach in tackling the problem of AMR. Therefore, unifying efforts to combat and overcome this alarming issue requires a many-sided approach. The key points of this mission are mainly highlighted in three major tasks, understanding the bacterial resistance mechanisms, in addition to the utilization of combinatorial therapeutic approaches for potential clinical options, and the discovery of novel antimicrobial agents and/or targets. The Research Topic entitled: "Combating Antimicrobial Resistance-A One Health Approach" harbors 25 published manuscripts that include 197 authors, scientists and researchers from worldwide renowned institutions and research centers. These manuscripts mainly focus on understanding the mechanisms of resistance in Gram-positive and Gram-negative MDR strains, address combination antimicrobial therapy as a potential treatment against Gram-positive and Gram-negative bacilli, and the discovery of novel antimicrobial agents with potential novel targets or new mode of actions. To understand the mechanisms of resistance in Gram-positive and Gram-negative MDR strains, the Research Topic consists of 13 outstanding manuscripts, reviews, and original research articles that aim to elucidate novel mechanisms of resistance in different MDR strains and widen our knowledge to further understand how Gram-positive and Gram-negative bacteria combat antimicrobial agents. With respect to Gram-positive bacteria, molecular epidemiological studies in Streptococcus pneumoniae from children with pneumonia in "Shanghai, China" provided the microbiology community with precise prevalence of serotype modifications and diversity in the emergence of MDR international clones, where the most common serotypes documented are 19F, 6A, 19A, 23F, 14, and 6B (Zhao et al.