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bioRxiv · 10.1101/2023.04.25.538267

Genomic characterization of a pandrug-resistant Klebsiella pneumoniae belonging to the high-risk ST11 in the Brazilian Amazon region

Fonseca, E.·Morgado, S.·Freitas, F.·Bighi, N.·Cipriano, R.·Vicente, A. C. P.
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Abstract

Pandrug-resistant (PDR) K. pneumoniae has been reported sporadically in many countries and remains rare in Brazil. The lack of genomic studies limits the comprehension of the determinants mostly involved with the PDR emergence in K. pneumoniae. This study aimed to unravel the main genetic determinants involved with the PDR background of a clinical ST11 K. pneumoniae recovered in the Brazilian Amazon region. The carbapenem-resistant Kp196 was submitted to WGS and its intrinsic and acquired resistome was assessed by CARD and comparison with wild-type genes. Kp196 resistome was composed of acquired resistance determinants and mutations in chromosomal genes. Among the formers, blaCTX-M-15 and blaNDM-1, blaOXA-9, blaOXA-1, aadA1, aacA4, strAB, aph(3)-VI, aac(3)-IId, qnrS1, qnrB1, oqxAB, dfrA14, sul2, catB3 were found in the vicinity of mobile genetic elements, which could contribute to their spread. Kp196 colistin resistance was multifactorial and attributed to modifications in ArnT (M114L/V117I/R372K), PhoQ (D150G), and the mgrB disruption by ISKpn25. Besides the presence of qnr and oqxAB genes, Kp196 also presented altered GyrA (S83I) and ParC (S80I). An in-block deletion in the repressor RamR, contributing to acrAB overexpression, and the presence of an enhanced-function AcrB variant (S966A), probably led to the Kp196 multidrug and tigecycline resistance. Insertions, in-block deletion, and missense mutations were involved with ompK35-36-37 inactivation, also accounting for the Kp196 multidrug resistance, including carbapenems. The Kp196 PDR profile, especially the carbapenem resistance, was due to the accumulation of different mechanisms, in which modifications in housekeeping genes accounted for a more stable resistome.

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Fonseca, E., Morgado, S., Freitas, F., Bighi, N., Cipriano, R., Vicente, A. C. P.. 2023-04-25. Genomic characterization of a pandrug-resistant Klebsiella pneumoniae belonging to the high-risk ST11 in the Brazilian Amazon region. https://doi.org/10.1101/2023.04.25.538267

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