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Global methicillin-resistant Staphylococcus aureus (MRSA) strains were dominated by few genetic lineages, suggesting their inherent advantage of competitive fitness. The information of genome evolution and population structures of prevalent MRSA strains can help gain a better understanding of the success of the pandemic clones. Whole-genome sequencing was performed in 340 MRSA isolates belonging to three prevalent lineages, including ST59 (129 isolates), ST239/241 (140 isolates), and ST5 (71 isolates), collected from 1996 to 2016 in Taiwan. The time-scaled phylogeny and evolutionary pathways were estimated by Bayesian analysis using Markov chain Monte Carlo. The toxome, resistome, and plasmids were characterized by screening the raw reads with a public database. ST59, ST239/241, and ST5 MRSA were estimated to emerge in 1974, 1979, and 1995, respectively, in Taiwan. ST59 evolved through two major pathways, generating two subclones in 1980 and 1984. Both ST59 subclones remained prevalent in the healthcare and community environments in late 2010s. ST239/241 diverged into three subclones, respectively, in 1989, 1993, and 1995. The 1995-emerging ST239 subclone predominated after 2000 by replacing two previous early subclones. ST5 could be subdivided into two clades within 3 years of introduction, but no substantial difference of genomic profiles was identified in the strains of distinct clades. Each of the three pandemic MRSA lineages harbored its own specific toxome, resistome, and plasmids. The frequently identified genetic diversities between the subclones of the same lineage were genes mediating immune evasion, leukocidins, enterotoxins, and resistance to aminoglycosides. In conclusion, MRSA ST59 and ST239/241 emerged in the 1970s and evolved drastically during 1980 and 1995, resulting in three successful subclones prevailing in Taiwan. ST5 was introduced late in 1995 without a significant genetic drift during 20 years of evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yang Lauderdale and Huang.)

The sulbactam resistance rate in Acinetobacter baumannii has increased worldwide. Previous reports have shown that the β-lactamase bla TEM-1 confers resistance to sulbactam in A. baumannii. The purpose of this study was to examine whether other β-lactamases, including the Acinetobacter-derived cephalosporinase (ADC), OXA-23, OXA-24/72, and OXA-58 families, also contribute to sulbactam resistance in A. baumannii. The correlation between these β-lactamases and the sulbactam minimal inhibitory concentration (MIC) was determined using A. baumannii clinical isolates from diverse clonality, which were collected in a nationwide surveillance program from 2002 to 2010 in Taiwan. A possible association between the genetic structure of ISAba1-bla ADC-30 and sulbactam resistance was observed because this genetic structure was detected in 97% of sulbactam-resistant strains compared with 10% of sulbactam-susceptible strains. Transformation of ISAba1-bla ADC-30 into susceptible strains increased the sulbactam MIC from 2 to 32 μg/ml, which required bla ADC-30 overexpression using an upstream promoter in ISAba1. Flow cytometry showed that ADC-30 production increased in response to sulbactam, ticarcillin, and ceftazidime treatment. This effect was regulated at the RNA level but not by an increase in the bla ADC-30 gene copy number as indicated by quantitative PCR. Purified ADC-30 decreased the inhibitory zone created by sulbactam or ceftazidime, similarly to TEM-1. In conclusion, ADC-30 overexpression conferred resistance to sulbactam in diverse clinical A. baumannii isolates.