Colistin Resistance in Aeromonas spp.

The increase in the use of antimicrobials such as colistin for the treatment of infectious diseases has led to the appearance of Aeromonas strains resistant to this drug. However, resistance to colistin not only occurs in the clinical area but has also been determined in Aeromonas isolates from the environment or animals, which has been determined by the detection of mcr genes that confer a resistance mechanism to colistin. The variants mcr-1, mcr-3, and mcr-5 have been detected in the genus Aeromonas in animal, environmental, and human fluids samples. In this article, an overview of the resistance to colistin in Aeromonas is shown, as well as the generalities of this molecule and the recommended methods to determine colistin resistance to be used in some of the genus Aeromonas.

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Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

BMC Microbiology ◽

10.1186/s12866-021-02250-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shixing Liu ◽

Renchi Fang ◽

Ying Zhang ◽

Lijiang Chen ◽

Na Huang ◽

...

Keyword(s):

Lipid A ◽

Efflux Pump ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Enterobacter Cloacae ◽

Resistance Mechanisms ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01586-18 ◽

2019 ◽

Vol 63 (3) ◽

Cited By ~ 18

Author(s):

Stefanie Gerson ◽

Jonathan W. Betts ◽

Kai Lucaßen ◽

Carolina Silva Nodari ◽

Julia Wille ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Lipid A ◽

Galleria Mellonella ◽

Resistance Mechanism ◽

Resistant Isolate ◽

Infection Model ◽

Colistin Resistance ◽

Strain Specificity ◽

Content Type

ABSTRACT Colistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of pmrC was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion ΔL9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.

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Functional Genome Screening to Elucidate the Colistin Resistance Mechanism

Scientific Reports ◽

10.1038/srep23156 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 8

Author(s):

Mohit Kumar ◽

Ashutosh Gupta ◽

Rajesh Kumar Sahoo ◽

Jayanti Jena ◽

Nagen Kumar Debata ◽

...

Keyword(s):

Resistance Mechanism ◽

Colistin Resistance ◽

Genome Screening ◽

Functional Genome

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Exogenous and Endogenous Phosphoethanolamine Transferases Differently Affect Colistin Resistance and Fitness in Pseudomonas aeruginosa

Frontiers in Microbiology ◽

10.3389/fmicb.2021.778968 ◽

2021 ◽

Vol 12 ◽

Author(s):

Matteo Cervoni ◽

Alessandra Lo Sciuto ◽

Chiara Bianchini ◽

Carmine Mancone ◽

Francesco Imperi

Keyword(s):

Pseudomonas Aeruginosa ◽

Lipid A ◽

Cell Envelope ◽

Resistance Mechanism ◽

Multidrug Resistant ◽

Transferase Activity ◽

Colistin Resistance ◽

Phosphoethanolamine Transferases ◽

Positively Charged ◽

Inducible Gene

Colistin represents a last-line treatment option for infections caused by multidrug resistant Gram-negative pathogens, including Pseudomonas aeruginosa. Colistin resistance generally involves the modification of the lipid A moiety of lipopolysaccharide (LPS) with positively charged molecules, namely phosphoethanolamine (PEtN) or 4-amino-4-deoxy-L-arabinose (Ara4N), that reduce colistin affinity for its target. Several lines of evidence highlighted lipid A aminoarabinosylation as the primary colistin resistance mechanism in P. aeruginosa, while the contribution of phosphoethanolamination remains elusive. PEtN modification can be due to either endogenous (chromosomally encoded) PEtN transferase(s) (e.g., EptA in P. aeruginosa) or plasmid borne MCR enzymes, commonly found in enterobacteria. By individually cloning eptA and mcr-1 into a plasmid for inducible gene expression, we demonstrated that MCR-1 and EptA have comparable PEtN transferase activity in P. aeruginosa and confer colistin resistance levels similar to those provided by lipid A aminoarabinosylation. Notably, EptA, but not MCR-1, negatively affects P. aeruginosa growth and, to a lesser extent, cell envelope integrity when expressed at high levels. Mutagenesis experiments revealed that PEtN transferase activity does not account for the noxious effects of EptA overexpression, that instead requires a C-terminal tail unique to P. aeruginosa EptA, whose function remains unknown. Overall, this study shows that both endogenous and exogenous PEtN transferases can promote colistin resistance in P. aeruginosa, and that PEtN and MCR-1 mediated resistance has no impact on growth and cell envelope homeostasis, suggesting that there may be no fitness barriers to the spread of mcr-1 in P. aeruginosa.

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Colistin resistance prevalence in Escherichia coli from domestic animals in intensive breeding farms of Jiangsu Province, China

10.1101/307983 ◽

2018 ◽

Cited By ~ 4

Author(s):

X. Zhang ◽

B. Zhang ◽

Z. Yu ◽

Y. Guo ◽

J. Wang ◽

...

Keyword(s):

Escherichia Coli ◽

Safety Issue ◽

Resistance Mechanism ◽

Domestic Animals ◽

Jiangsu Province ◽

Resistant Bacteria ◽

Colistin Resistance ◽

E Coli ◽

Chromogenic Agar ◽

Breeding Farms

AbstractThe global dissemination of colistin resistance has received a great deal of attention. Recently, the plasmid-mediated colistin resistance encoded by mcr-1 and mcr-2 genes in Escherichia coli (E.coli) strains from animals, food, and patients in China have been reported continuously. To make clear the colisin resistance and mcr gene spread in domestic animals in Jiangsu Province, we collected fecael swabs from pigs, chicken and cattle at different age distributed in intensive feeding farms. The selected chromogenic agar and mcr-PCR were used to screen the colisin resistance and mcr gene carriage. Colistin resistant E.coli colonies were identified from 54.25 % (440/811) pig faecal swabs, from 35.96 % (443/1232) chicken faecal swabs, and 26.92 % (42/156) from cattle faecal swabs. Of all the colisin resistant E.coli colonies, the positive amplifications of mcr-1 were significantly higher than mcr-2. The mcr-1 prevalence was 68.86 % (303/440) in pigs, 87.58 % (388/443) in chicken, and 71.43 % (30/42), compared with 46.82 % (206/440) in pigs, 14.90 % (66/443) in chicken, and 19.05 % (8/42) in cattle of prevalence of mcr-2. Co-occurrence of mcr-1 and mcr-2 was identified in 20 % (88/440) in pigs, 7.22 % (32/443) in chickens, and in 9.52 % (4/42) cattle. These data indicate that mcr was the most important colistin resistance mechanism. Interventions and alternative options are necessary to minimise further dissemination of mcr between food-producing animals and human.IMPORTANCEColistin is recognized one of the last defence lines for the treatment of highly resistant bacteria, but the emergence of resistance that conferred by a transferable plasmid-mediated mcr genes to this vital antibiotic is extremely disturbing. Here, we used E. coli as an index to monitor drug resistance in domestic animals (pigs, chicken and cattle). It was found that the colistin resistance widely occurred at all ages of domestic animals and the mcr-dependent mechanism dominated in E.coli. We also found that the elder and adult animals were a reservoir of resistant strains, suggesting a potential food safety issue and greater public health problems.

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Characterization of resistance mechanisms of Enterobacter cloacae Complex Co-resistant to Carbapenem and Colistin

10.21203/rs.3.rs-38056/v1 ◽

2020 ◽

Author(s):

Tieli Zhou ◽

Shixing Liu ◽

Renchi Fang ◽

Ying Zhang ◽

Lijiang Chen ◽

...

Keyword(s):

Membrane Protein ◽

Outer Membrane ◽

Lipid A ◽

Efflux Pump ◽

Medical Center ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Enterobacter Cloacae ◽

Colistin Resistance ◽

Carbapenemase Gene

Abstract Background: The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains.Methods: Nineteen ECC isolates co-resistant to carbapenems and colistin were collected from a regional medical center in China. Carbapenemase gene, extended-spectrum β-lactamase gene, AmpC cephalosporinase gene ampC, mcr series genes, and ecr gene were detected by PCR. Expression levels of outer membrane protein OmpC/OmpF and efflux pump protein AcrA/AcrB were investigated. And the structural modification of lipid A of 19 ECC strains was analyzed.Results: This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). And the mechanism of colistin resistance is increaseing expression of acrA in the efflux pump AcrAB-TolC alone (5 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found.Conclusions: This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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A rare case of Colistin-resistant Salmonella Enteritidis meningitis in an HIV-seropositive patient

BMC Infectious Diseases ◽

10.1186/s12879-019-4391-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 10

Author(s):

Roxanne Rule ◽

Nontombi Mbelle ◽

John Osei Sekyere ◽

Marleen Kock ◽

Anwar Hoosen ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Infection Control ◽

Salmonella Enteritidis ◽

Resistance Mechanism ◽

Genomic Analysis ◽

Young Male ◽

Empiric Therapy ◽

Adverse Outcomes ◽

Colistin Resistance ◽

Rare Finding

Abstract Background Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa. Case presentation We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism. Conclusion Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.

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CHROMOSOMAL LOCATIONS OF mcr-1 IN Klebsiella pneumoniae AND Enterobacter cloacae FROM DOGS

Taiwan Veterinary Journal ◽

10.1142/s168264851972003x ◽

2019 ◽

Vol 45 (03) ◽

pp. 79-84

Author(s):

MING-HUANG CHANG ◽

GUAN-JUN CHEN ◽

DAN-YUAN LO

Keyword(s):

Escherichia Coli ◽

Early Detection ◽

Klebsiella Pneumoniae ◽

Companion Animals ◽

Resistance Mechanism ◽

Enterobacter Cloacae ◽

Insertion Sequences ◽

Colistin Resistance ◽

Molecular Surveillance ◽

Klebsiella Spp

In November 2015, the emergence of a novel plasmid-mediated colistin resistance mechanism was described. So far, there are only two relevant published reports focused solely on Escherichia coli and Salmonella in Taiwan. This paper describes the emergence of colistin-resistant Klebsiella pneumoniae and Enterobacter cloacae clinical isolates harboring mcr-1 on chromosomes in Taiwan. All four mcr-1-positive isolates were from 63 Klebsiella spp., and the isolated Enterobacter spp. were from diseased dogs and cats at Veterinary Teaching Hospital, National Chiayi University. These four isolates were resistant to colistin, amoxicillin, doxycycline and oxytetracycline, and all mcr-1 genes were located on the chromosome, without any flanking ISApl1 or other insertion sequences. The findings suggest that, in addition to food animals and humans, companion animals can serve as reservoirs of mcr-1, adding another layer of complexity to the rapidly evolving epidemiology of plasmid-mediated colistin resistance in the community. Hence we consider it essential to continue to survey resistance to colistin in these bacteria. Continuous microbiological and molecular surveillance is necessary to assist in early detection and minimize the dissemination of mcr-1.

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