scholarly journals A novel mobile RND-type efflux pump gene cluster, tmexC3D2-toprJ3, confers tigecycline resistance in Pseudomonas alcaligenes

2021 ◽  
Author(s):  
Shotaro Maehana ◽  
Ryotaro Eda ◽  
Nagi Niida ◽  
Aki Hirabayashi ◽  
Kouji Sakai ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Resistance Genes ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Genomic Studies ◽  
Rnd Efflux Pumps ◽  
Pseudomonas Alcaligenes ◽  
Hospital Sewage

Tigecycline exhibits promising activity against multidrug-resistant gram-negative bacteria (MDR-GNB). However, mobile tigecycline resistance genes, such as tmexCD-toprJ encoding RND efflux pumps, have emerged. Here, we identified a novel tmexC3D2-toprJ3 gene cluster in tigecycline- and carbapenem-nonsusceptible Pseudomonas alcaligenes isolates from hospital sewage in Japan in 2020. tmexC3D2-toprJ3 and two copies of blaIMP-1 were located on the chromosome. This suggests that diverse tmexCD-toprJ-like genes have spread among MDR-GNB worldwide and further epidemiological genomic studies are needed.

A Tobramycin Vector Enhances Synergy and Efficacy of Efflux Pump Inhibitors against Multidrug-Resistant Gram-Negative Bacteria

2017 ◽  
Vol 60 (9) ◽  
pp. 3913-3932 ◽  
Author(s):  
Xuan Yang ◽  
Sudeep Goswami ◽  
Bala Kishan Gorityala ◽  
Ronald Domalaon ◽  
Yinfeng Lyu ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Efflux Pump Inhibitors

scholarly journals Species Diversity of Environmental GIM-1-Producing Bacteria Collected during a Long-Term Outbreak

2016 ◽  
Vol 82 (12) ◽  
pp. 3605-3610 ◽  
Author(s):  
Andreas F. Wendel ◽  
Sofija Ressina ◽  
Susanne Kolbe-Busch ◽  
Klaus Pfeffer ◽  
Colin R. MacKenzie
Keyword(s):  
Resistance Genes ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Environmental Sampling ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Content Type

ABSTRACTReports of outbreaks concerning carbapenemase-producing Gram-negative bacteria in which the main source of transmission is the hospital environment are increasing. This study describes the results of environmental sampling in a protracted polyspecies metallo-beta-lactamase GIM-1 outbreak driven by plasmids and bacterial clones ofEnterobacter cloacaeandPseudomonas aeruginosain a tertiary care center. Environmental sampling targeting wet locations (especially sinks) was carried out on a surgical intensive care unit and on a medical ward on several occasions in 2012 and 2013. We were able to demonstrate 43blaGIM-1-carrying bacteria (mainly nonfermenters but alsoEnterobacteriaceae) that were either related or unrelated to clinical strains in 30 sinks and one hair washbasin. GIM-1 was found in 12 different species, some of which are described here as carriers of GIM-1. Forty out of 43 bacteria displayed resistance to carbapenems and, in addition, to various non-beta-lactam antibiotics. Colistin resistance was observed in twoE. cloacaeisolates with MICs above 256 mg/liter. TheblaGIM-1gene was harbored in 12 different class 1 integrons, some without the typical 3′ end. TheblaGIM-1gene was localized on plasmids in five isolates.In vitroplasmid transfer by conjugation was successful in one isolate. The environment, with putatively multispecies biofilms, seems to be an important biological niche for multidrug-resistant bacteria and resistance genes. Biofilms may serve as a “melting pot” for horizontal gene transfer, for dissemination into new species, and as a reservoir to propagate future hospital outbreaks.IMPORTANCEIn Gram-negative bacteria, resistance to the clinically relevant broad-spectrum carbapenem antibiotics is a major public health concern. Major reservoirs for these resistant organisms are not only the gastrointestinal tracts of animals and humans but also the (hospital) environment. Due to the difficulty in eradicating biofilm formation in the latter, a sustained dissemination of multidrug-resistant bacteria from the environment can occur. In addition, horizontal transfer of resistance genes on mobile genetic elements within biofilms adds to the total “resistance gene pool” in the environment. To gain insight into the transmission pathways of a rare and locally restricted carbapenemases resistance gene (blaGIM-1), we analyzed the genetic background of theblaGIM-1gene in environmental bacteria during a long-term polyspecies outbreak in a German hospital.

scholarly journals Investigation of urban birds as source of β-lactamase-producing Gram-negative bacteria in Marseille city, France

2019 ◽  
Vol 61 (1) ◽  
Author(s):  
Edgarthe Priscilla Ngaiganam ◽  
Isabelle Pagnier ◽  
Wafaa Chaalal ◽  
Thongpan Leangapichart ◽  
Selma Chabou ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Urban Birds ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Stool Samples

Abstract Background We investigate here the presence of multidrug-resistant bacteria isolated from stool samples of yellow-legged gulls and chickens (n = 136) in urban parks and beaches of Marseille, France. Bacterial isolation was performed on selective media, including MacConkey agar with ceftriaxone and LBJMR medium. Antibiotic resistance genes, including extended-spectrum β-lactamases (ESBL) (i.e. blaCTX-M, blaTEM and blaSHV), carbapenemases (blaKPC, blaVIM, blaNDM, blaOXA-23, blaOXA-24, blaOXA-48 and blaOXA-58) and colistin resistance genes (mcr-1 to mcr-5) were screened by real-time PCR and standard PCR and sequenced when found. Results Of the 136 stools samples collected, seven ESBL-producing Gram-negative bacteria (BGN) and 12 colistin-resistant Enterobacteriaceae were isolated. Among them, five ESBL-producing Escherichia coli and eight colistin-resistant Hafnia alvei strains were identified. Four blaTEM-1 genes were detected in yellow-legged gulls and chickens. Three CTX-M-15 genes were detected in yellow-legged gulls and pigeons, and one CTX-M-1 in a yellow-legged gull. No mcr-1 to mcr-5 gene were detected in colistin-resistant isolates. Genotyping of E. coli strains revealed four different sequence types already described in humans and animals and one new sequence type. Conclusions Urban birds, which are believed to have no contact with antibiotics appear as potential source of ESBL genes. Our findings highlight the important role of urban birds in the proliferation of multidrug-resistant bacteria and also the possible zoonotic transmission of such bacteria from wild birds to humans.

scholarly journals IS26 mediate the acquisition of tigecycline resistance gene cluster tmexCD1-toprJ1 by IncHI1B-FIB plasmids in Klebsiella pneumoniae and Klebsiella quasipneumoniae from food market sewage

2020 ◽  
Author(s):  
Miao Wan ◽  
Xun Gao ◽  
Luchao Lv ◽  
Zhongpeng Cai ◽  
Jian-Hua Liu
Keyword(s):  
Klebsiella Pneumoniae ◽  
Gene Cluster ◽  
Resistance Gene ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Resistance Gene Cluster ◽  
Carbapenem Resistant ◽  
Food Market ◽  
Carbapenem Resistant Enterobacteriaceae

Tigecycline and colistin are considered 20 as the final options for the treatment of infections caused by multidrug-resistant (MDR) gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (1).…

scholarly journals Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates

2003 ◽  
Vol 376 (3) ◽  
pp. 801-805 ◽  
Author(s):  
Monique MALLÉA ◽  
Abdallah MAHAMOUD ◽  
Jacqueline CHEVALIER ◽  
Sandrine ALIBERT-FRANCO ◽  
Pierre BROUANT ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Microbial Pathogens ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
High Level ◽  
Antibiotic Efflux

Over the last decade, MDR (multidrug resistance) has increased worldwide in microbial pathogens by efflux mechanisms, leading to treatment failures in human infections. Several Gram-negative bacteria efflux pumps have been described. These proteinaceous channels are capable of expelling structurally different drugs across the envelope and conferring antibiotic resistance in various bacterial pathogens. Combating antibiotic resistance is an urgency and the blocking of efflux pumps is an attractive response to the emergence of MDR phenotypes in infectious bacteria. In the present study, various alkylaminoquinolines were tested as potential inhibitors of drug transporters. We showed that alkylaminoquinolines are capable of restoring susceptibilities to structurally unrelated antibiotics in clinical isolates of MDR Gram-negative bacteria. Antibiotic efflux studies indicated that 7-nitro-8-methyl-4-[2´-(piperidino)ethyl]aminoquinoline acts as an inhibitor of the AcrAB–TolC efflux pump and restores a high level of intracellular drug concentration. Inhibitory activity of this alkylaminoquinoline is observed on clinical isolates showing different resistance phenotypes.

Prevalence of Carbapenemase Genes, qacE, qacEΔ1 and cepA in Multidrug-Resistant Gram-Negative Bacteria with Different Susceptibility to Chlorhexidine

2020 ◽  
Vol 19 (5) ◽  
pp. 49-60
Author(s):  
K. G. Kosyakova ◽  
N. B. Esaulenko ◽  
O. A. Kameneva ◽  
S. P. Kazakov ◽  
A. Y. Dubinina ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Multidrug Resistant ◽  
World Health ◽  
Dynamic Monitoring ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Health Organization

Relevance The World Health Organization has provided a list of resistant bacteria that pose the greatest threat to society. Among them, the most important (critically high priority level) are Pseudomonas aeruginosa and Acinetobacter baumannii strains resistant to carbapenems, as well as enterobacteriaceae producing extended spectrum beta-lactamases and carbapenemases.Aim. To conduct a comparative analysis of the sensitivity to chlorhexidine of multiply-resistant gram-negative bacteria, the causative agents of infectious conditions in patients of various medical organizations, and to study the relationship between the presence of resistance genes and the minimum inhibitory concentration of chlorhexidine.Materials & methods. The study included 138 Gram-negative multidrug-resistant strains isolated during 2018–2019 from various clinical specimens. Susceptibility of the isolates to antibiotics were determined using Vitek-2 compact and Phoenix М50, susceptibility to chlorhexidine were determined by agar dilution method. The resistance genes were detected by the real-time PCR method.Results. The lowest level of resistance to chlorhexidine was determined in E. coli strains (MIC90 16 mg/l), other strains were highly resistant: MIC90 of P. aeruginosa and A. baumannii – 128 mg/l, K. pneumoniae, E. cloacae и P. mirabilis – 256 mg/l. The highest frequency of detection of carbapenemase genes observed in K. pneumoniae strains – 56.0% and P. aeruginosa – 48.1%. High prevalence of cepA gene was found out (the strains of enterobacteria – 47.8%, A. baumannii – 42.9%), genes qacE, qacEΔ1 were more often detected in non-fermenting Gram-negative bacteria then in enterobacteria. Conclusion. According to the results of our study, we did not reveal a significant correlation between the presence or absence of resistance genes and MIC of chlorhexidine in Gram-negative bacteria. However, taking into account complex mechanism of the adaptive response of bacteria to the effects of chlorhexidine, and to implement the concept of preventing health care-associated infections, it is proposed to continue dynamic monitoring of the resistance of microorganisms to antiseptics, disinfectants and antibiotics.

scholarly journals Plasmids Shape the Current Prevalence of tmexCD1-toprJ1 among Klebsiella pneumoniae in Food Production Chains

mSystems ◽  
2021 ◽  
Author(s):  
Kai Peng ◽  
Qian Wang ◽  
Yi Yin ◽  
Yan Li ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Human Health ◽  
Food Production ◽  
Antibacterial Agents ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Current Prevalence

Tigecycline, the first member of the glycylcycline class of antibacterial agents, is frequently used to treat complicated infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria. The emergence of a novel plasmid-mediated efflux pump, TmexCD1-ToprJ1, conferring resistance to multiple antimicrobials, including tigecycline, poses a huge risk to human health.

scholarly journals Benzydamine Reverses TMexCD-TOprJ-Mediated High-Level Tigecycline Resistance in Gram-Negative Bacteria

2021 ◽  
Vol 14 (9) ◽  
pp. 907
Author(s):  
Ziwen Tong ◽  
Tianqi Xu ◽  
Tian Deng ◽  
Jingru Shi ◽  
Zhiqiang Wang ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Galleria Mellonella ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Intracellular Accumulation ◽  
Gram Negative ◽  
Resistance Nodulation Division ◽  
High Level

Recently, a novel efflux pump gene cluster called tmexCD1-toprJ1 and its variants have been identified, which undermine the antibacterial activity of tigecycline, one of the last remaining options effective against multidrug-resistant (MDR) Gram-negative bacteria. Herein, we report the potent synergistic effect of the non-steroidal anti-inflammatory drug benzydamine in combination with tigecycline at sub-inhibitory concentrations against various temxCD-toprJ-positive Gram-negative pathogens. The combination of benzydamine and tigecycline killed all drug-resistant pathogens during 24 h of incubation. In addition, the evolution of tigecycline resistance was significantly suppressed in the presence of benzydamine. Studies on the mechanisms of synergism showed that benzydamine disrupted the bacterial proton motive force and the functionality of this kind of novel plasmid-encoded resistance-nodulation-division efflux pump, thereby promoting the intracellular accumulation of tigecycline. Most importantly, the combination therapy of benzydamine and tigecycline effectively improved the survival of Galleria mellonella larvae compared to tigecycline monotherapy. Our findings provide a promising drug combination therapeutic strategy for combating superbugs carrying the tmexCD-toprJ gene.

scholarly journals Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria

2016 ◽  
Vol 60 (5) ◽  
pp. 3215-3218 ◽  
Author(s):  
Wentao Ni ◽  
Yanjun Li ◽  
Jie Guan ◽  
Jin Zhao ◽  
Junchang Cui ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Resistant Strains ◽  
Efflux Pump Inhibitors ◽  
Time Kill

ABSTRACTWe tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially inAcinetobacter baumanniiandStenotrophomonas maltophilia. These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP.

Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Da’san M. M. Jaradat ◽  
Nehaya Al-Karablieh ◽  
Basmah H. M. Zaarer ◽  
Wenyi Li ◽  
Khalil K.Y. Saleh ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Low Concentrations ◽  
Bacterial Mutants ◽  
Drug Efflux Pumps ◽  
Gastrointestinal Peptides

Abstract Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the Enterobacteriaceae bacteria, Escherichia coli and Erwinia amylovora. GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria E. coli TG1 and E. amylovora 1189 strains. The effect was comparable to bacterial mutants lacking the inner and outer membrane efflux pump factor proteins AcrB and TolC. While GIP was devoid of direct antimicrobial activity, it has a potent membrane depolarizing effect, and at low concentrations, it significantly potentiated the activity of eight antibiotics and bile salt by reducing MICs by 4-8-fold in E. coli TG1 and 4-20-fold in E. amylovora 1189. GIP can thus be regarded as an antimicrobial adjuvant with potential for augmenting the available antibiotic arsenal.

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