Expected Plazomicin Susceptibility in India Based on the Prevailing Aminoglycoside Resistance Mechanisms in Gram-Negative Organisms Derived from Whole-Genome Sequencing

Ochrobactrum species are non-enteric, Gram-negative organisms that are closely related to the genus Brucella. Since the designation of the genus in 1988, several distinct species have now been characterised and implicated as opportunistic pathogens in multiple outbreaks. Here, we examine the genus, its members, diagnostic tools used for identification, data from recent Ochrobactrum whole genome sequencing and the pathogenicity associated with reported Ochrobactrum infections. This review identified 128 instances of Ochrobactrum spp. infections that have been discussed in the literature. These findings indicate that infection review programs should consider investigation of possible Ochrobactrum spp. outbreaks if these bacteria are clinically isolated in more than one patient and that Ochrobactrum spp. are more important pathogens than previously thought.

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Identification and Characterization of a Novel Chromosomal Aminoglycoside 2′-N-Acetyltransferase, AAC(2′)-If, From an Isolate of a Novel Providencia Species, Providencia wenzhouensis R33

Frontiers in Microbiology ◽

10.3389/fmicb.2021.711037 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kexin Zhou ◽

Jialei Liang ◽

Xu Dong ◽

Peiyao Zhang ◽

Chunlin Feng ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Resistance Gene ◽

Genome Sequencing ◽

Resistance Mechanisms ◽

Parameter Analysis ◽

Resistant Bacteria ◽

Comparative Genomic ◽

Molecular Characteristics ◽

Whole Genome ◽

Aminoglycoside Resistance

Multidrug-resistant bacteria from different sources have been steadily emerging, and an increasing number of resistance mechanisms are being uncovered. In this work, we characterized a novel resistance gene named aac(2′)-If from an isolate of a novel Providencia species, Providencia wenzhouensis R33 (CCTCC AB 2021339). Susceptibility testing and enzyme kinetic parameter analysis were conducted to determine the function of the aminoglycoside 2′-N-acetyltransferase. Whole-genome sequencing and comparative genomic analysis were performed to elucidate the molecular characteristics of the genome and the genetic context of the resistance gene-related sequences. Among the functionally characterized resistance genes, AAC(2′)-If shares the highest amino acid sequence identity of 70.79% with AAC(2′)-Ia. AAC(2′)-If confers resistance to several aminoglycoside antibiotics, showing the highest resistance activity against ribostamycin and neomycin. The recombinant strain harboring aac(2′)-If (pUCP20-aac(2′)-If/DH5α) showed 256- and 128-fold increases in the minimum inhibitory concentration (MIC) levels to ribostamycin and neomycin, respectively, compared with those of the control strains (DH5α and pUCP20/DH5α). The results of the kinetic analysis of AAC(2′)-If were consistent with the MIC results of the cloned aac(2′)-If with the highest catalytic efficiency for ribostamycin (kcat/Km ratio = [3.72 ± 0.52] × 104 M–1⋅s–1). Whole-genome sequencing demonstrated that the aac(2′)-If gene was located on the chromosome with a relatively unique genetic environment. Identification of a novel aminoglycoside resistance gene in a strain of a novel Providencia species will help us find ways to elucidate the complexity of resistance mechanisms in the microbial population.

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Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA

Clinical Microbiology and Infection ◽

10.1016/j.cmi.2017.02.021 ◽

2017 ◽

Vol 23 (8) ◽

pp. 574.e7-574.e14 ◽

Cited By ~ 44

Author(s):

B.J. Metcalf ◽

S. Chochua ◽

R.E. Gertz ◽

P.A. Hawkins ◽

J. Ricaldi ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Streptococcus Agalactiae ◽

Resistance Mechanisms ◽

Whole Genome ◽

Short Read ◽

The Usa

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Whole-genome sequencing of carbapenem-resistant gram-negative bacteria in patients with cirrhosis

10.1055/s-0040-1721949 ◽

2021 ◽

Author(s):

TG Schultze ◽

PG Ferstl ◽

D Villinger ◽

M Hogardt ◽

WO Bechstein ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Carbapenem Resistant

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Whole-Genome Sequences of Brucella melitensis Strain QY1, Isolated from Sheep in Gansu, China

Genome Announcements ◽

10.1128/genomea.00896-17 ◽

2017 ◽

Vol 5 (35) ◽

Cited By ~ 4

Author(s):

Xiaoan Cao ◽

Zhaocai Li ◽

Zhongzi Lou ◽

Baoquan Fu ◽

Yongsheng Liu ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Human Disease ◽

Brucella Melitensis ◽

Whole Genome ◽

Negative Bacterium ◽

Genome Sequences ◽

Gram Negative ◽

Content Type ◽

Wild Mammals

ABSTRACT The facultative intracellular Gram-negative bacterium Brucella melitensis causes brucellosis in domestic and wild mammals, and it is a dominant pathogen responsible for human disease. This study reports the whole-genome sequencing of B. melitensis strain QY1, isolated from sheep suffering from abortion and arthritis in 2015 in Gansu, China.

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Ceftolozane/Tazobactam Resistance and Mechanisms in Carbapenem-Nonsusceptible Pseudomonas aeruginosa

mSphere ◽

10.1128/msphere.01026-20 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Jocelyn Qi-Min Teo ◽

Jie Chong Lim ◽

Cheng Yee Tang ◽

Shannon Jing-Yi Lee ◽

Si Hui Tan ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Molecular Epidemiology ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Antimicrobial Agents ◽

Resistance Mechanisms ◽

Cross Resistance ◽

Whole Genome ◽

Genotypic Resistance ◽

Content Type

ABSTRACT This study established the in vitro activity of ceftolozane/tazobactam (C/T) and its genotypic resistance mechanisms by whole-genome sequencing (WGS) in 195 carbapenem-nonsusceptible Pseudomonas aeruginosa (CNSPA) clinical isolates recovered from Singapore between 2009 and 2020. C/T susceptibility rates were low, at 37.9%. Cross-resistance to ceftazidime/avibactam was observed, although susceptibility to the agent was slightly higher, at 41.0%. Whole-genome sequencing revealed that C/T resistance was largely mediated by the presence of horizontally acquired β-lactamases, especially metallo-β-lactamases. These were primarily disseminated in well-recognized high-risk clones belonging to sequence types (ST) 235, 308, and 179. C/T resistance was also observed in several non-carbapenemase-producing isolates, in which resistance was likely mediated by β-lactamases and, to a smaller extent, mutations in AmpC-related genes. There was no obvious mechanism of resistance observed in five isolates. The high C/T resistance highlights the limited utility of the agent as an empirical agent in our setting. Knowledge of local molecular epidemiology is crucial in determining the potential of therapy with novel agents. IMPORTANCE Pseudomonas aeruginosa infection is one of the most difficult health care-associated infections to treat due to the ability of the organism to acquire a multitude of resistance mechanisms and express the multidrug resistance phenotype. Ceftolozane/tazobactam (C/T), a novel β-lactam/β-lactamase inhibitor combination, addresses an unmet medical need in patients with these multidrug-resistant P. aeruginosa infections. Our findings demonstrate geographical variation in C/T susceptibility owing to the distinct local molecular epidemiology. This study adds on to the growing knowledge of C/T resistance, particularly mutational resistance, and will aid in the design of future β-lactams and β-lactamase inhibitors. WGS proved to be a useful tool to understand the P. aeruginosa resistome and its contribution to emerging resistance in novel antimicrobial agents.

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Whole genome sequencing for antimicrobial resistance mechanisms, virulence factors and clonality in invasive Streptococcus agalactiae blood culture isolates recovered in Australia

Pathology ◽

10.1016/j.pathol.2020.06.006 ◽

2020 ◽

Vol 52 (6) ◽

pp. 694-699

Author(s):

Adam G. Stewart ◽

Delaney Burnard ◽

David Sowden ◽

David McMillan

Keyword(s):

Antimicrobial Resistance ◽

Blood Culture ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Virulence Factors ◽

Streptococcus Agalactiae ◽

Resistance Mechanisms ◽

Whole Genome

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Heteroresistance to Amikacin in Carbapenem-Resistant Klebsiella pneumoniae Strains

Frontiers in Microbiology ◽

10.3389/fmicb.2021.682239 ◽

2021 ◽

Vol 12 ◽

Author(s):

Feiyang Zhang ◽

Qin Li ◽

Jiawei Bai ◽

Manlin Ding ◽

Xiangjin Yan ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Reverse Transcription ◽

Pcr Analysis ◽

Whole Genome ◽

Single Nucleotide Variants ◽

Aminoglycoside Resistance ◽

Quantitative Reverse Transcription Pcr ◽

Reverse Transcription Pcr

Heteroresistance can lead to treatment failure and is difficult to detect by the methods currently employed by clinical laboratories. The aim of this study was to investigate the prevalence of the amikacin-heteroresistant Klebsiella pneumoniae strains and explore potential amikacin heteroresistance mechanism through whole-genome sequencing (WGS) and quantitative reverse-transcription PCR (qRT-PCR). In this study, 13 isolates (8.39%) were considered as amikacin-heteroresistant K. pneumoniae strains among a total of 155 K. pneumoniae strains. The majority of the heterogeneous phenotypes (11/13, 84.61%) was unstable and the minimal inhibitory concentrations (MICs) fully or partially reverted back to the level of susceptibility of the parental isolate. The frequency of heteroresistant subpopulation ranged from 2.94×10−7 to 5.59×10−6. Whole-genome sequencing and single-nucleotide variants (SNVs) analysis showed that there were different nucleotide and resultant amino acid alterations among an amikacin-heteroresistant strain S38 and the resistant subpopulation S38L in several genes. Quantitative reverse-transcription PCR analysis revealed that the increased expression of aminoglycoside resistance genes detected in amikacin-heteroresistant K. pneumoniae strains might be associated with amikacin heteroresistance. The findings raise concerns for the emergence of amikacin-heteroresistant K. pneumoniae strains and the use of amikacin as therapy for the treatment of multidrug-resistant K. pneumoniae strains.

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