Effects of Simulated Microgravity on Acquired Antibiotic Resistance in Klebsiella pneumoniae Exposed to Trace Antibiotic.

ABSTRACT

Objective: The purpose of this study is to gain a better understanding of the impact of microgravity on antibiotic resistance. Methods: K. pneumoniae original (KPO) strain was cultured under either simulated microgravity (SMG) conditions with background antibiotic exposure (SMGA) for the experimental strain or a normal gravity condition with background antibiotic exposure (NGA) for the control strain. The K. pneumoniae original (KPO) strain was also cultured under normal gravity (NG) as an additional control. Antibiotic susceptibility was evaluated prior to their incubation under SMGA, NGA, or NG conditions. After 20 cycles of incubation, antibiotic susceptibility, genomic, transcriptomic, and proteomic tests were conducted on them. Results: SMGA and NGA strains both showed resistance to ciprofloxacin and intermediate resistance to levofloxacin. Genes associated with antibiotic resistance of Klebsiella pneumoniae, including acrB, oqxB, oqxA, ompC, ompF, and tolC were found to be differently expressed between SMGA and NGA strains or between SMGA and NG strains. It was found that the biggest family of genes in the differently expressed gene (DEG) cluster between SMGA and NGA and between SMGA and NG was the same, paaBCDFGHI, but with opposite change direction, i.e., downregulation between SMGA and NGA strains, while upregulation between SMGA and NG strains. Besides, the top-ranking functional descriptions in terms of the number of DEGs whether between SMGA and NGA or between SMGA and NG were "amino acid transport and metabolism", "carbohydrate transport and metabolism", "transcription", and "inorganic ion transport and metabolism". Two pathways of "citrate cycle (TCA cycle)" and "oxidative phosphorylation" were significantly enriched by DEGs both between SMGA and NGA and between SMGA and NG. Conclusion: Our study confirmed that low levels of antibiotics present in SMG can select for resistant K. pneumoniae strains. However, SMG did not alter the antibiotic resistance in K. pneumoniae induced by exposure to trace antibiotic.