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Mari TOHYA, Teruo KIRIKAECorresponding author: Teruo KirikaeDepartment of Microbiology, Juntendo University School of Medicine2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanTEL: +81-3-5802-1041　FAX: +81-3-5684-7830　E-mail: t-kirikae@juntendo.ac.jpResearch of the 5th Alumni Scientific Award for Medical Student, Juntendo University School of Medicine〔Received　Jan. 8, 2022〕〔Accepted　Jan. 28, 2022〕J-STAGE Advance published date: Jun. 9, 2022Copyright © 2022 The Juntendo Medical Society. This is an open access article distributed under the terms of Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original source is properly credited. doi: 10.14789/jmj.JMJ21-0057-RJuntendo Medical Journal2022. 68(3), 200-207Key words: Providencia rettgeri, Providencia stuartti, metallo-β-lactamaseReviewsEmergence of Carbapenem-resistant Clinical Isolates of Providencia SpeciesTaxonomy of the Providencia genusProvidencia, a genus of Gram-negative and non- spore forming bacteria, was originally assigned to the family Enterobacteriaceae, but has recently been assigned to the family Morganellaceae1). Species of Providencia genus have been isolated from many vertebrate and invertebrate animals, including humans and insects2-4), and causes opportunistic infections in humans5). To date, 10 species belonging to the genus Providencia have been identified: P. alcalifaciens, P. burhodogranariea, P. heimbachae, P. huaxiensis, P. rettgeri, P. rustigianii, P. sneebia, P. stuartii, P. thailandensis and P. vermicola. Of these 10 species of Providencia, five, P. alcalifaciens, Department of Microbiology, Juntendo University School of Medicine, Tokyo, JapanP. friedericiana (synonym of P. rustigianii), P. rettgeri, P. stuartii and P. vermicola, were isolated from humans, with three of these, P. alcalifaciens, P. rettgeri and P. stuartii, likely to be clinically important5, 6). A phylogenetic tree based on whole genome sequences of the 10 Providencia species revealed that these species consist of three clusters, with the five species isolated from humans, being spread among these three clusters (Figure 1). These findings indicate that the genus Providencia does not have a subgenus associated with human infections. The five species were found to have specific genes associated with human infections, such as genes encoding adherence and invasion factors.Shu IWATA, Tatsuya TADA, Satoshi OSHIRO, Tomomi HISHINUMA, 　Providencia is a genus of Gram-negative and non-spore forming bacteria belonging to the family Morganellaceae, which causes opportunistic infections in humans. Of the 10 Providencia species identified to date, three, P. alcalifaciens, P. rettgeri and P. stuartii, are clinically important. P. alcalifaciens causes diarrhea, including outbreaks arising from food-borne infections, and P. stuartii and P. rettgeri have been found to cause hospital acquired urinary tract infections. Four isolates of P. rettgeri and one isolate of P. stuartii were obtained from urine samples of five patients in Japan in 2018. All five isolates were highly resistant to carbapenems. Three isolates harbored blaIMP-70, encoding a variant of IMP-1 metallo-β-lactamase, with two amino acid substitutions (Val67Phe and Phe87Val), one isolate harbored two copies of blaIMP-1 and one isolate harbored blaIMP-11. Expression of blaIMP-70 conferred carbapenem resistance in Escherichia coli. Recombinant IMP-10, an IMP-1 variant with Val67Phe but without Phe87Val, had significant higher hydrolytic activities against meropenem than recombinant IMP-1, indicating that the Val67Phe amino acid substitution alters activities against meropenem in IMP-70. These results suggest that Providencia species. become more highly resistant to carbapenems by acquisition of two copies of blaIMP-1 or by mutations in blaIMP that result in amino acid substitutions, such as blaIMP-70.200