Prevotella are Gram-negative anaerobic bacteria that are a part of the normal flora colonizing mucous membranes of the oral cavity, gastrointestinal tract, and female genitourinary tract. These organisms can be pathogenic and frequently cause infections, such as odontogenic, head and neck, intra-abdominal, and gynecological infections [1,2]. Prevotella species are more susceptible to antimicrobial agents than Bacteroides species, which are frequently isolated from various anaerobic infection sites. However, antimicrobial-resistant Prevotella isolates, especially those resistant to β-lactams, have become increasingly common [1,[3], [4], [5], [6], [7], [8]]. Elucidating the underlying mechanisms that contribute to the emergence and spread of antimicrobial resistance in Prevotella species is crucial for developing effective treatment strategies for infections caused by these organisms.

The production of β-lactamases is the most common resistance mechanism to β-lactam antibiotics in Gram-negative anaerobes. β-lactam resistance among Prevotella species is frequently attributed to the production of the CfxA β-lactamase [[9], [10], [11]]. This enzyme, a member of subgroup 2e β-lactamases (class A), can hydrolyze penicillins and broad-spectrum cephalosporins [12]. The cfxA gene, which encodes the CfxA β-lactamase, has six variants with several point mutations in their nucleotide sequences [9,[12], [13], [14]]. These genotypes, denoted cfxA, cfxA2, cfxA3, cfxA4, cfxA5, and cfxA6, have been reported in some genera such as Bacteroides, Prevotella, and Capnocytophaga [9,[12], [13], [14]]. Although the alleles of the cfxA gene have been detected in various bacterial species [15], these have not been comprehensively described for Prevotella species. Moreover, the relationship between the cfxA sequence variation and the antimicrobial susceptibility profile of the CfxA-producing isolates remains unclear.

Besides β-lactam resistance by β-lactamase genes, various antimicrobial resistance genes have been reported in anaerobes. Resistance genes, such as tetQ, which confers resistance to tetracycline [16], and ermF, which is associated with resistance to macrolides, lincosamides, and streptogramins [17], have been identified in Prevotella species [7,18,19]. These resistance genes are frequently linked to conjugative transposons and can be exchanged among anaerobic bacteria by horizontal gene transfer [20]. cfxA genes have been reported to be transmitted horizontally by mobile genetic elements, and this could lead to the spread of antimicrobial resistance [14,15,[21], [22], [23]]. Therefore, the emergence of multidrug-resistant Prevotella species harboring cfxA genes may become a major public health threat in the future.

In the present study, we analyzed the relationship between cfxA sequence variations and antimicrobial susceptibilities of the CfxA-producing Prevotella isolates. Further, we investigated the prevalence of other resistance genes (tetQ, ermF, and nim) and the associated antimicrobial susceptibility profiles among multidrug-resistant Prevotella isolates. The results obtained in this study enrich our understanding of cfxA variants and their distribution, as well as the associated antimicrobial susceptibility profiles, which can advise prevention measures against the spread of antimicrobial-resistant Prevotella species.