Andersen Camilla, Gabrielaite Migle, Nørskov-Lauritsen Niels
Department of Clinical Microbiology, Aarhus University Hospital, DK-8200 Aarhus, Denmark.
Center for Genomic Medicine, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Microorganisms. 2022 Feb 11;10(2):420. doi: 10.3390/microorganisms10020420.
species are emerging pathogens in cystic fibrosis with inherent resistance to several classes of antimicrobial agents. We exposed strains with wild-type antimicrobial susceptibility to ticarcillin and generated mutants with broad β-lactam resistance. Within the detection limit of the assay, the capability to develop mutational resistance was strain-specific and reproducible. Mutational resistance was observed for all three tested strains of , for one of seven strains of , and for none of five strains of . All mutants were resistant to piperacillin-tazobactam, while minimal inhibitory concentration of several other β-lactams increased 4-32-fold. Whole genome sequencing identified 1-4 non-synonymous mutations in known genes per mutant. All mutants encoded amino acid substitutions in cell wall recycling proteins, primarily Mpl, and the observed resistance is probably caused by hyperproduction of OXA-114-like β-lactamases. Related, but not identical substitutions were detected in clinical strains expressing acquired antimicrobial resistance.
某些菌种是囊性纤维化中的新兴病原体，对几类抗菌药物具有固有抗性。我们使具有野生型抗菌敏感性的菌株暴露于替卡西林，并产生了具有广泛β-内酰胺抗性的突变体。在该检测方法的检测限内，产生突变抗性的能力具有菌株特异性且可重复。在所有三个测试的菌株中观察到突变抗性，在七个菌株中的一个中观察到突变抗性，而在五个菌株中均未观察到突变抗性。所有突变体均对哌拉西林-他唑巴坦耐药，而其他几种β-内酰胺的最低抑菌浓度增加了4至32倍。全基因组测序确定每个突变体在已知基因中有1至4个非同义突变。所有突变体在细胞壁循环蛋白（主要是Mpl）中编码氨基酸替代，观察到的抗性可能是由OXA-114样β-内酰胺酶的过量产生引起的。在表达获得性抗菌抗性的临床菌株中检测到相关但不相同的替代。
