scholarly journals Can We Exploit β-Lactamases Intrinsic Dynamics for Designing More Effective Inhibitors?

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 833
Author(s):  
Eleonora Gianquinto ◽  
Donatella Tondi ◽  
Giulia D'Arrigo ◽  
Loretta Lazzarato ◽  
Francesca Spyrakis
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Design ◽  
Infectious Diseases ◽  
Binding Site ◽  
Catalytic Efficiency ◽  
Gram Negative Bacteria ◽  
Allosteric Inhibitors ◽  
Gram Negative ◽  
Protein Size ◽  
Allosteric Sites

β-lactamases (BLs) represent the most frequent cause of antimicrobial resistance in Gram-negative bacteria. Despite the continuous efforts in the development of BL inhibitors (BLIs), new BLs able to hydrolyze the last developed antibiotics rapidly emerge. Moreover, the insurgence rate of effective mutations is far higher than the release of BLIs able to counteract them. This results in a shortage of antibiotics that is menacing the effective treating of infectious diseases. The situation is made even worse by the co-expression in bacteria of BLs with different mechanisms and hydrolysis spectra, and by the lack of inhibitors able to hit them all. Differently from other targets, BL flexibility has not been deeply exploited for drug design, possibly because of the small protein size, for their apparent rigidity and their high fold conservation. In this mini-review, we discuss the evidence for BL binding site dynamics being crucial for catalytic efficiency, mutation effect, and for the design of new inhibitors. Then, we report on identified allosteric sites in BLs and on possible allosteric inhibitors, as a strategy to overcome the frequent occurrence of mutations in BLs and the difficulty of competing efficaciously with substrates. Nevertheless, allosteric inhibitors could work synergistically with traditional inhibitors, increasing the chances of restoring bacterial susceptibility towards available antibiotics.

Antimicrobial Activity of Iron-Halide Complexes Against Gram-Positive and Gram-Negative Bacteria

2020 ◽  
Author(s):  
Nusrat Abedin ◽  
Abdullah Hamed A Alshehri ◽  
Ali M A Almughrbi ◽  
Olivia Moore ◽  
Sheikh Alyza ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Resistance ◽  
Extracellular Dna ◽  
Antibiofilm Activity ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
Antimicrobial Substances ◽  
Mammalian Cell Lines

Antimicrobial resistance (AMR) has become one of the more serious threats to the global health. The emergence of bacteria resistant to antimicrobial substances decreases the potencies of current antibiotics. Consequently, there is an urgent and growing need for the developing of new classes of antibiotics. Three prepared novel iron complexes have a broad-spectrum antimicrobial activity with minimum bactericidal concentration (MBC) values ranging from 3.5 to 10 mM and 3.5 to 40 mM against Gram-positive and Gram-negative bacteria with antimicrobial resistance phenotype, respectively. Time-kill studies and quantification of the extracellular DNA confirmed the bacteriolytic mode of action of the iron-halide compounds. Additionally, the novel complexes showed significant antibiofilm activity against the tested pathogenic bacterial strains at concentrations lower than the MBC. The cytotoxic effect of the complexes on different mammalian cell lines show sub-cytotoxic values at concentrations lower than the minimum bactericidal concentrations.

Prevalence and Antimicrobial Resistance of Gram-Negative Bacteria Isolates in Shellfish Samples from Two River Estuaries in South-South Nigeria

2021 ◽  
Vol 11 (09) ◽  
pp. 428-443
Author(s):  
Nsikan Samuel Udoekong ◽  
Bassey Enya Bassey ◽  
Anne Ebri Asuquo ◽  
Otobong Donald Akan ◽  
Casmir Ifeanyichukwu Cajetan Ifeanyi
Keyword(s):  
Antimicrobial Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals PATIENTS' MICROFLORA COMPARATIVE CHARACTERISTICS OF DIFFERENT DEPARTMENTS AT THE NATIONAL HOSPITAL OF PEDIATRICS IN HANOI, VIETNAM

2019 ◽  
pp. 43-48
Author(s):  
L.V. Kataeva ◽  
A.P. Rebeshchenko ◽  
T.F. Stepanova ◽  
O.V. Posoiuznykh ◽  
Le Thanh Hai ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Infectious Diseases ◽  
Hospital Environment ◽  
Clinical Samples ◽  
Gram Negative Bacteria ◽  
National Hospital ◽  
Statistical Research ◽  
Gram Positive ◽  
Gram Negative

We studied the microflora structure and resistance gathered from the biomaterial of patients and the environment objects of various departments at the National hospital of Pediatrics in Hanoi. 140 clinical samples of biomaterials from 74 patients treated in the intensive care unit, the infectious diseases and the gastroenterology departments were studied. A systematic approach including microbiological, epidemiological and statistical research methods was used in carrying out the study. Bacteria of the Enterobacteriaceae family (38.5 per cent) prevailed in the biomaterial of intensive care unit patients. Nonfermentative Gram-negative bacteria (46.5 per cent) occupied the leading positions in the infectious diseases department and Gram-positive bacteria (39.3 per cent) were in the gastroenterology department. Gram-positive flora (60.2 per cent in the intensive care unit and 50.7 per cent in the infectious diseases department) prevailed in the microflora structure gathered from hospital environment objects. We identified the prevalence of bacteria of the genus Enterobacteriaceae and non-fermentative Gram-negative bacteria with a wide spectrum of resistance in the departments of the National Hospital of Pediatrics.

scholarly journals Whole-Genome Sequencing of Gram-Negative Bacteria Isolated From Bovine Mastitis and Raw Milk: The First Emergence of Colistin mcr-10 and Fosfomycin fosA5 Resistance Genes in Klebsiella pneumoniae in Middle East

2021 ◽  
Vol 12 ◽  
Author(s):  
Yasmine H. Tartor ◽  
Norhan K. Abd El-Aziz ◽  
Rasha M. A. Gharieb ◽  
Hend M. El Damaty ◽  
Shymaa Enany ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Genome Sequencing ◽  
Bovine Milk ◽  
Bovine Mastitis ◽  
Raw Milk ◽  
Whole Genome ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli

Antimicrobial resistance is a major concern in the dairy industry. This study investigated the prevalence, antimicrobial resistance phenotypes, and genome sequencing of Gram-negative bacteria isolated from clinical (n = 350) and subclinical (n = 95) bovine mastitis, and raw unpasteurized milk (n = 125). Klebsiella pneumoniae, Aeromonas hydrophila, Enterobacter cloacae (100% each), Escherichia coli (87.78%), and Proteus mirabilis (69.7%) were the most prevalent multidrug-resistant (MDR) species. Extensive drug-resistance (XDR) phenotype was found in P. mirabilis (30.30%) and E. coli (3.33%) isolates. Ten isolates (four E. coli, three Klebsiella species and three P. mirabilis) that displayed the highest multiple antibiotic resistance (MAR) indices (0.54–0.83), were exposed to whole-genome sequencing (WGS). Two multilocus sequence types (MLST): ST2165 and ST7624 were identified among the sequenced E. coli isolates. Three E. coli isolates (two from clinical mastitis and one from raw milk) belonging to ST2165 showed similar profile of plasmid replicon types: IncFIA, IncFIB, IncFII, and IncQ1 with an exception to an isolate that contained IncR, whereas E. coli ST7624 showed a different plasmid profile including IncHI2, IncHI2A, IncI1α, and IncFII replicon types. ResFinder findings revealed the presence of plasmid-mediated colistin mcr-10 and fosfomycin fosA5 resistance genes in a K. pneumoniae (K1) isolate from bovine milk. Sequence analysis of the reconstructed mcr-10 plasmid from WGS of K1 isolate, showed that mcr-10 gene was bracketed by xerC and insertion sequence IS26 on an IncFIB plasmid. Phylogenetic analysis revealed that K1 isolate existed in a clade including mcr-10-harboring isolates from human and environment with different STs and countries [United Kingdom (ST788), Australia (ST323), Malawi (ST2144), Myanmar (ST705), and Laos (ST2355)]. This study reports the first emergence of K. pneumoniae co-harboring mcr-10 and fosA5 genes from bovine milk in the Middle East, which constitutes a public health threat and heralds the penetration of the last-resort antibiotics. Hence, prudent use of antibiotics in both humans and animals and antimicrobial surveillance plans are urgently required.

Antimicrobial Resistance in Some Gram-Negative Bacteria Isolated from the Bovine Ejaculate

2013 ◽  
Vol 48 (3) ◽  
pp. 525-528 ◽  
Author(s):  
C Kilburn ◽  
DJ Rooks ◽  
AJ McCarthy ◽  
RD Murray
Keyword(s):  
Antimicrobial Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals Antimicrobial Susceptibility Pattern of Gram-Negative Bacterial Isolates from Raw Chicken Meat Samples

2019 ◽  
Vol 6 ◽  
pp. 89-95
Author(s):  
Neha Gautam ◽  
Rojan Poudel ◽  
Binod Lekhak ◽  
Milan Kumar Upreti
Keyword(s):  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Chicken Meat ◽  
Food Microbiology ◽  
Diffusion Method ◽  
Resistance Pattern ◽  
Kathmandu Valley ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Meat Samples

Objectives: This research aims to study the microbial quality of chicken meat available in retail shop of Kathmandu Valley. Methods:  This Study was conducted from June to December 2018 in three different districts of Kathmandu Valley. Samples were collected in sterile plastic bags, labeled properly and stored in an icebox and transported to the Food Microbiology laboratory of Golden Gate International College.  During sample preparation, 25 grams of each sample was taken and transferred to sterile flasks containing 225 ml of buffered peptone water. Potential pathogenic Gram-negative bacteria were isolated by using respective selective media and identified by biochemical test. Antibiotic susceptibility profile of isolates was carried out by Kirby-Bauer disc diffusion method according to CLSI 2017 guideline. Results: Of total 81 chicken meat samples processed; 201 Gram negative bacteria were isolated.  E. coli (100%) was the dominant Gram-negative isolates, followed by Citrobacter spp (62.96%), Pseudomonas spp (40.74%), Proteus spp (19.75%), Salmonella spp (16.04%) and Klebsiella spp (8.64%) respectively. No any multidrug isolates were detected. Conclusion: The study showed that the raw chicken meat samples of Kathmandu valley was highly contaminated with Gram negative potential pathogenic bacteria. Antimicrobial resistance pattern shown by the isolates may indicates that there is not overuse of drug in animals and the less chance of risk of increasing antimicrobial resistance.

scholarly journals The carbon source influences the efflux pump-mediated antimicrobial resistance in clinically important Gram-negative bacteria

2012 ◽  
Vol 67 (4) ◽  
pp. 921-927 ◽  
Author(s):  
N. A. Villagra ◽  
J. A. Fuentes ◽  
M. R. Jofre ◽  
A. A. Hidalgo ◽  
P. Garcia ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Carbon Source ◽  
Efflux Pump ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Gram Negative Bacteria ◽  
National Surveillance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.

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