Pathogenic Escherichia coli Possess Elevated Growth Rates under Exposure to Sub-Inhibitory Concentrations of Azithromycin

Abstract

Antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the ten major threats to global health. Advances in technology, including whole-genome sequencing, have provided new insights into the origin and mechanisms of AMR. However, our understanding of the short-term impact of antimicrobial pressure and resistance on the physiology of bacterial populations is limited. We aimed to investigate morphological and physiological responses of clinical isolates of E. coli under short-term exposure to key antimicrobials. We performed whole-genome sequencing on twenty-seven E. coli isolates isolated from children with sepsis to evaluate their AMR gene content. We assessed their antimicrobial susceptibility profile and measured their growth dynamics and morphological characteristics under exposure to varying concentrations of ciprofloxacin, ceftriaxone, tetracycline, gentamicin, and azithromycin. AMR was common, with all organisms resistant to at least one antimicrobial; a total of 81.5% were multi-drug-resistant (MDR). We observed an association between resistance profile and morphological characteristics of the E. coli over a three-hour exposure to antimicrobials. Growth dynamics experiments demonstrated that resistance to tetracycline promoted the growth of E. coli under antimicrobial-free conditions, while resistance to the other antimicrobials incurred a fitness cost. Notably, antimicrobial exposure heterogeneously suppressed bacterial growth, but sub-MIC concentrations of azithromycin increased the maximum growth rate of the clinical isolates. Our results outline complex interactions between organism and antimicrobials and raise clinical concerns regarding exposure of sub-MIC concentrations of specific antimicrobials.

Discerning the role of polymyxin B nonapeptide in restoring the antibacterial activity of azithromycin against antibiotic-resistant Escherichia coli

“…It is noteworthy that ermB containing strains had higher AZT MICs (>128 μg/ml) than majority of mphA harboring strains (MIC: 32 to >128 μg/ml), which could affect the likelihood of success of synergy with PMBN. Unfortunately, the sole effect of ermB gene could not be explored as none of the strains tested in this study possess this gene alone, which is a common limitation encountered in previous studies ( Tuan-Anh et al, 2020 ). The latter study reported that strains harboring both ermB with mphA genes had significantly higher MICs than strains without ermB gene, in agreement with our results.…”

Large-scale analysis of putative plasmids in clinical multidrug-resistant Escherichia coli isolates from Vietnamese patients

“…We eliminated studies that did not perform whole-genome sequencing using Illumina platforms or did not publish raw sequencing data, leaving 3 studies for inclusion. Raw sequencing data of 751 multidrug-resistant E. coli strains previously published by Roberts et al (2022) (ENA Bioproject: PRJEB29424 and PRJEB28400), Hirabayashi et al (2021) (provided by the authors), and Tuan-Anh et al (2020) (ENA Bioproject PRJEB39354) were downloaded from the European Nucleotide Archive (ENA) database. Sixteen samples were from environmental surfaces (environmental isolates) and were collected at the National Hospital for Tropical Diseases, Hanoi, Vietnam.…”

“…One duplicate isolate (NHP1391) was excluded from the analysis. The two isolates (MH13 and MH17) from the study by Hirabayashi et al (2021) were from the Military Hospital 103 in Hanoi, and the 27 isolates from the study by Tuan-Anh et al (2020) were from the Children’s Hospital 1 in Ho Chi Minh city. Two E. coli isolates (TN1393 and XP817) were from our laboratory (NCBI SRA BioProject: PRJNA857185) and were from two patients hospitalized in the Saint Paul Hospital and the 108 Military Central Hospital, respectively.…”

“…The E. coli isolates from the study by Roberts et al (2022) were classified into two phenotypes, ESBL-producing isolates and CR isolates, in function of their growth on selective media. The phenotype classification of the other isolates was based (i) on the antimicrobial susceptibility test results extracted from the studies by Hirabayashi et al (2021) and Tuan-Anh et al (2020) , and (ii) for the two isolates from our laboratory (TN1393 and XP817), on antimicrobial susceptibility testing performed using ampicillin, amoxicillin-clavulanic acid, amikacin, piperacillin, ticarcillin, ticarcillin-clavulanic acid, cefalexin, cefoxitin, ceftazidime, colistin, fosfomycin, ofloxacin, imipenem, penicillin, and trimethoprim-sulfamethoxazole and the Kirby Bauer disk diffusion method, as previously described ( EUCAST, 2020 ). In total, 4/751 strains were classified as non-ESBL-producing strains (see also Supplementary Table S1 ).…”

The effects of emerging contaminants on the behaviour of Acinetobacter calcoaceticus derived from biofilms

“…Kim et al 59 demonstrated that the previous adaptation of E. coli to formic acid also resulted in a reduction in the doubling time. Moreover, Tuan-Anh et al 60 also described an increased growth rate for pathogenic E. coli exposed to sub-inhibitory concentrations of azithromycin.…”