Unravelling the mechanisms of albicidin resistance in Acinetobacter baumannii IMT51508

Introduction:

Antimicrobial resistance has emerged as a major clinical and public health challenge worldwide. According to one recent report, antimicrobial resistance caused 5 million human deaths in 2019 and estimated up to 10 million deaths by 2050 [1].

Albicidin is a promising antibacterial peptide that inhibits the bacterial DNA gyrase's activity [2]. It is extensively studied in SalmonellaTyphimurium and Escherichia coli. The reported resistance mechanisms included degradation by the endopeptidase AlbD, and binding of albicidin through MerR-like transcriptional regulator AlbA [3]. The goal of our study is to identify the mechanism of albicidin resistance to ESKAPE pathogens that are leading cause of nosocomial infections. The study is particularly focused to understand the resistance mechanism in a nosocomial pathogen Acinetobacter baumannii IMT51508.

Methodology:

The study is designed to measure the Minimum Inhibitory Concentration (MIC) of albicidin in corresponding bacterium, leading to laboratory evolution and Next generation sequencing (NGS) of evolved eight independent mutants. We also measured the cross-resistance of bacteria to other antibiotics and effect of antimicrobial on bacterial growth through resistogram and time kill assay respectively.

Results:

The experiments deduced the MIC of IMT51508 0.06250 µg/mL followed by evolution of bacteria to 64xMIC (4mg/mL) of albicidin. However, considerate genetic analysis demonstrated that eight independent mutants have developed the resistance in DUF445 domain containing protein (YjiN) and additionally, three out of eight mutants have also mutated the DNA gyrase subunit A (gyrA). However, mutagenesis experiments are in process to investigate the explicit mechanism of resistance. Interestingly, the resistogram analysis predicted the elevated level of resistance to ciprpfloxacin in all independently evolved mutants.

Conclusion:

In conclusion, the perspective study has potential to understand the diversified strategies of bacterial resistance mechanisms to a potential peptide antibiotic. The better understanding will ultimately lead to design specified and precise resistance coping approach.