Metronidazole resistance and nim genes in anaerobes: A review

• Published in: Anaerobe Vol. 55; pp. 40 - 53
• Main Authors: Alauzet, Corentine, Lozniewski, Alain, Marchandin, Hélène
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2019; Elsevier Masson
• Subjects: Anaerobes; Life Sciences; Metronidazole; Microbiology and Parasitology; nim gene; Resistance; Resistance; nim gene; Anaerobes; Metronidazole
• ISSN: 1075-9964; 1095-8274
• DOI: 10.1016/j.anaerobe.2018.10.004

Acquired resistance to metronidazole, a 5-nitroimidazole drug largely used worldwide in the empirical treatment of infections caused by anaerobes, is worrisome, especially since such resistance has been described in multidrug-resistant anaerobic bacteria. In anaerobes, acquired resistance to metronidazole may be due to a combination of various and complex mechanisms. Among them, nim genes, possibly located on mobile genetic elements, encode nitro-imidazole-reductases responsible for drug inactivation. Since the first description of Nim proteins about 25 years ago, more nim genes have been identified; currently 11 nim genes are known (nimA to nimK). Mostly reported in Bacteroides fragilis group isolates, nim genes are now described in a variety of anaerobic genera encompassing the 4 main groups of Gram-negative and Gram-positive bacilli and cocci, with variable expression ranging from phenotypically silent to low-level or high-level resistance to metronidazole. This review describes the trends of metronidazole resistance rates among anaerobes over the past 20 years and summarizes current knowledge on mechanisms involved in this resistance. It also provides an update on the phylogenetic and geographical distribution of nim genes, the mechanisms involved in their expression and regulation, and their role in metronidazole resistance. •Metronidazole is a drug of choice for treatment of infections caused by anaerobes.•MTZ acquired resistance may associate several mechanisms including Nim proteins.•10 nim genes of variable expression (silent→various resistance levels) are described.•nim genes are present in a wide range of bacterial phyla.•nim genes are part of the genetic content of multidrug resistant anaerobes.