scholarly journals Deep Mutational Scanning Reveals the Active-Site Sequence Requirements for the Colistin Antibiotic Resistance Enzyme MCR-1

mBio ◽  
2021 ◽  
Author(s):  
Zhizeng Sun ◽  
Timothy Palzkill
Keyword(s):  
Antibiotic Resistance ◽  
Active Site ◽  
Multidrug Resistant ◽  
Multidrug Resistant Pathogens ◽  
Emergence Of Resistance ◽  
Sequence Requirements ◽  
Active Site Sequence

Polymyxin antibiotics are used as last-line antibiotics in treating infections caused by multidrug-resistant pathogens. However, widespread use of polymyxins has led to the emergence of resistance.

scholarly journals Molecules that Inhibit Bacterial Resistance Enzymes

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 43 ◽  
Author(s):  
Yuan Liu ◽  
Ruichao Li ◽  
Xia Xiao ◽  
Zhiqiang Wang
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Resistance ◽  
Enzyme Inhibitors ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Clinical Challenge ◽  
Potential Inhibitors ◽  
The Impact ◽  
Emergence Of Resistance ◽  
Secreted Enzymes

Antibiotic resistance mediated by bacterial enzymes constitutes an unmet clinical challenge for public health, particularly for those currently used antibiotics that are recognized as “last-resort” defense against multidrug-resistant (MDR) bacteria. Inhibitors of resistance enzymes offer an alternative strategy to counter this threat. The combination of inhibitors and antibiotics could effectively prolong the lifespan of clinically relevant antibiotics and minimize the impact and emergence of resistance. In this review, we first provide a brief overview of antibiotic resistance mechanism by bacterial secreted enzymes. Furthermore, we summarize the potential inhibitors that sabotage these resistance pathways and restore the bactericidal activity of inactive antibiotics. Finally, the faced challenges and an outlook for the development of more effective and safer resistance enzyme inhibitors are discussed.

Distribution of Pathogens Involved in Infections in Oncological Patients and their Antibiotic Resistance Profile

2020 ◽  
Vol 70 (12) ◽  
pp. 4287-4294
Keyword(s):  
Antibiotic Resistance ◽  
Cancer Patients ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Resistance Pattern ◽  
Antibiotic Resistance Profile ◽  
Oncological Patients ◽  
Eastern European Countries ◽  
Klebsiella Spp

Cancer is the second leading cause of death in Romania and worldwide. Cancer patients are at increasing risk of acquiring bacterial infection with multi-resistant germs, including multidrug-resistant (MDR) strains of Gram-negative bacteria involved in nosocomial infection. Romania is one of the South-Eastern European countries with one of the highest prevalence rates of MDR pathogens. To determine the resistance pattern of bacterial profile and antibiotic resistance pattern in cancer patients admitted at the County Emergency Clinical Hospital Craiova, Romania. A retrospective study of bacterial pathogens was carried out on 90 adult cancer patients admitted from January to December 2018. The analysis of the resistance patterns for the action of the appropriate antibiotics was performed using Vitek 2 Compact system and diffusion method. In this study there were analysed 92 samples from 90 oncological patients (37-86 years). A total of 157 bacterial isolates were obtained, of which 37 strains of Staphylococcus aureus (23.56%), followed by Streptococcus pneumoniae (23- 14.64%), Klebsiella spp. and Escherichia coli (22 - 14,01%). The most common isolates were from respiratory tract (86 isolates - 54.77%). High rates of MDR were found for E. coli (63.63%), MRSA (61,11%) and Klebsiella spp. (54,54%), while one third of the isolated strains of Pseudomonas aeruginosa, Acinetobacter spp. and Proteus spp. were MDR. The findings of this study may be the basis for further more extensive studies highlighting the germs involved in the infectious pathology of cancer patients, in order to determine the antimicrobial resistance and to improve the methods of prophylaxis and treatment. Keywords: multidrug resistance (MDR), cancer patients, bacterial pathogen

Antimicrobial Resistance and Presence of Class 1 Integrons Among Different Serotypes of Salmonella spp. Recovered From Children with Diarrhea in Tehran, Iran

2020 ◽  
Vol 20 (2) ◽  
pp. 160-166
Author(s):  
Seyedeh Hanieh Eshaghi Zadeh ◽  
Hossein Fahimi ◽  
Fatemeh Fardsanei ◽  
Mohammad Mehdi Soltan Dallal
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
Salmonella Spp ◽  
Class 1 Integron ◽  
Class 1 Integrons ◽  
Food Borne ◽  
Class 1 ◽  
Resistance Patterns ◽  
C 30

Background: Salmonellosis is a major food-borne disease worldwide. The increasing prevalence of antimicrobial resistance among food-borne pathogens such as Salmonella spp. is concerning. Objective: The main objective of this study is to identify class 1 integron genes and to determine antibiotic resistance patterns among Salmonella isolates from children with diarrhea. Methods: A total of 30 Salmonella isolates were recovered from children with diarrhea. The isolates were characterized for antimicrobial susceptibility and screened for the presence of class 1 integron genes (i.e. intI1, sulI1, and qacEΔ1). Results: The most prevalent serotype was Enteritidis 36.7%, followed by Paratyphi C (30%), and Typhimurium (16.7%). The highest rates of antibiotic resistance were obtained for nalidixic acid (53.3%), followed by streptomycin (40%), and tetracycline (36.7%). Regarding class 1 integrons, 36.7%, 26.7%, and 33.3% of the isolates carried intI1, SulI, and qacEΔ1, respectively, most of which (81.8%) were multidrug-resistant (MDR). Statistical analysis revealed that the presence of class 1 integron was significantly associated with resistance to streptomycin and tetracycline (p = 0.042). However, there was no association between class 1 integron and other antibiotics used in this study (p > 0.05). Conclusion: The high frequency of integron class 1 gene in MDR Salmonella strains indicates that these mobile genetic elements are versatile among different Salmonella serotypes, and associated with reduced susceptibility to many antimicrobials.

scholarly journals 99. Effectiveness of Antibiotic Prophylaxis Among Patients Undergoing Elective Transurethral Resection of the Prostate in the Era of Antibiotic Resistance

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S179-S180
Author(s):  
Thana Khawcharoenporn ◽  
Pimjira Kanoktipakorn
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Prophylaxis ◽  
Transurethral Resection ◽  
Tertiary Care ◽  
Multidrug Resistant ◽  
Prophylactic Antibiotics ◽  
Care Hospital ◽  
Extended Spectrum Beta Lactamase ◽  
Observational Cohort

Abstract Background Data existing on effectiveness of antibiotic prophylaxis (AP) for transurethral resection of the prostate (TURP) are limited in the era of antibiotic resistance. Methods A 4-year prospective observational cohort study was conducted among patients undergoing TURP in an academic tertiary-care hospital during 2016–2019. Patients were excluded if pre-operative (pre-op) urine cultures were not sent or grew mixed (>2) organisms, or they had pre-op urinary tract infection (UTI) or lost follow-up after TURP. Appropriateness of AP was defined as 1) correct dosing and duration and narrowest spectrum according to the hospital AP guidelines and local epidemiology and 2) being active against uropathogens isolated from the pre-op culture. Primary outcome was the rate of UTI within 30 days post TURP compared between appropriate antibiotic prophylaxis (AAP) and inappropriate antibiotic prophylaxis (IAP) groups. Results 342 patients were screened and 61 were excluded. Of the 281 patients included, 139 (49%) received AAP and 142 (51%) received IAP. The reasons for IAP were prescribing too broad-spectrum antibiotics (57%), inactive antibiotics (41%) and incorrect dosing (2%). Pre-op urine cultures were no growth in 148 patients (53%). Among the 133 positive urine cultures with 144 isolates, Escherichia coli (52%) was the most commonly isolated. Thirty-one percent of these 144 isolates produced extended-spectrum beta-lactamase (ESBL) and 23 (16%) isolates were multidrug-resistant. The resistant rates of Enterobacteriaceae were 73% for ciprofloxacin, 65% for TMP-SMX and 46% for ceftriaxone. The two most commonly prescribed prophylactic antibiotics were ceftriaxone (51%) and ciprofloxacin (34%). The rate of UTI within 30 days post-TURP was significantly higher in IAP group compared to AAP group (47% vs 27%; P< 0.001). Prescribing inactive prophylactic antibiotics was the independent factor associated with 30-day post-TURP UTI (adjusted odds ratio 2.88; P=0.001). Conclusion Appropriate antibiotic prophylaxis significantly reduced UTI within 30 days of elective TURP. Obtaining pre-op urine culture and prescribing an active prophylactic agent are critical for preventing post-TURP UTI in the era of antibiotic resistance. Disclosures All Authors: No reported disclosures

scholarly journals Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

2021 ◽  
Vol 14 (5) ◽  
pp. 420
Author(s):  
Tanveer Ali ◽  
Abdul Basit ◽  
Asad Mustafa Karim ◽  
Jung-Hun Lee ◽  
Jeong-Ho Jeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Active Site ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Meca Gene ◽  
Resistance Mechanism ◽  
Ligand Docking ◽  
Clinical Samples ◽  
Allosteric Site ◽  
Methicillin Resistant

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.

scholarly journals Analysis of 56,348 Genomes Identifies the Relationship between Antibiotic and Metal Resistance and the Spread of Multidrug-Resistant Non-Typhoidal Salmonella

2021 ◽  
Vol 9 (7) ◽  
pp. 1468
Author(s):  
Gavin J. Fenske ◽  
Joy Scaria
Keyword(s):  
Antibiotic Resistance ◽  
Foodborne Pathogen ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Metal Resistance ◽  
Group 3 ◽  
Group 2 ◽  
Occurrence Matrix ◽  
Genome Assemblies ◽  
Group 1

Salmonella enterica is common foodborne pathogen that generates both enteric and systemic infections in hosts. Antibiotic resistance is common is certain serovars of the pathogen and of great concern to public health. Recent reports have documented the co-occurrence of metal resistance with antibiotic resistance in one serovar of S. enterica. Therefore, we sought to identify possible co-occurrence in a large genomic dataset. Genome assemblies of 56,348 strains of S. enterica comprising 20 major serovars were downloaded from NCBI. The downloaded assemblies were quality controlled and in silico serotyped to ensure consistency and avoid improper annotation from public databases. Metal and antibiotic resistance genes were identified in the genomes as well as plasmid replicons. Co-occurrent genes were identified by constructing a co-occurrence matrix and grouping said matrix using k-means clustering. Three groups of co-occurrent genes were identified using k-means clustering. Group 1 was comprised of the pco and sil operons that confer resistance to copper and silver, respectively. Group 1 was distributed across four serovars. Group 2 contained the majority of the genes and little to no co-occurrence was observed. Metal and antibiotic co-occurrence was identified in group 3 that contained genes conferring resistance to: arsenic, mercury, beta-lactams, sulfonamides, and tetracyclines. Group 3 genes were also associated with an IncQ1 class plasmid replicon. Metal and antibiotic co-occurrence from group 3 genes is mostly isolated to one clade of S. enterica I 4,[5],12:i:-.

scholarly journals Green synthesis of silk sericin-embedded silver nanoparticles and their antibacterial application against multidrug-resistant pathogens

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Md. Abdullah Al Masud ◽  
Hamid Shaikh ◽  
Md. Shamsul Alam ◽  
M. Minnatul Karim ◽  
M. Abdul Momin ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Green Synthesis ◽  
Bombyx Mori ◽  
Multidrug Resistant ◽  
Visible Spectroscopy ◽  
Silk Sericin ◽  
X Ray ◽  
Synthesis Strategy ◽  
Uv Visible ◽  
Multidrug Resistant Pathogens

Abstract Background The green synthesis strategy of metallic nanoparticles (NPs) has become popular due to being environmentally friendly. Stable silver nanoparticles (AgNPs) have been synthesized by natural products such as starch, soy protein, various extract of leaves, barks, and roots functioning both as reducing and stabilizing agents. Likewise, silk sericin (SS) is a globular protein discarded in the silk factory might be used for NP synthesis. In this research, we focus on the green synthesis and stabilization of AgNPs by SS as well as assessment of their antibacterial activities against some drug-resistant pathogen. Results SS was extracted from Bombyx mori silkworm cocoons in an aqueous medium. 17 w/w% of dry sericin powder with respect to the cocoon’s weight was obtained by freeze-drying. Furthermore, AgNPs conjugated to sericin, i.e., SS-capped silver nanoparticles (SS-AgNPs) were synthesized by easy, cost-effective, and environment-friendly methods. The synthesized SS-AgNPs were characterized by UV-visible spectroscopy, Fourier-transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy, transmission electron microscopy (TEM), and X-ray diffraction measurement. It has been found from the absorbance of UV-visible spectroscopy that a higher percent of SS-AgNPs was obtained at a higher concentration of silver nitrate solution. FTIR-ATR spectra showed that the carboxylate groups obtained from silk sericin act as a reducing agent for the synthesis of silver nanoparticles, while NH2+ and COO− act as a stabilizer of AgNPs. The X-ray diffractogram of SS-AgNPs was quite different from AgNO3 and sericin due to a change in the crystal structure. The diameter of AgNPs was around 20–70 nm observed using TEM. The synthesized SS-AgNPs exhibited strong antibacterial activity against multidrug-resistant pathogens, Escherichia coli and Pseudomonas aeruginosa. Minimal inhibitory/bactericidal concentrations against E. coli and P. aeruginosa were 20μg/mL. Conclusions This study encourages the use of Bombyx mori for the ecofriendly synthesis of SS-AgNPs to control multidrug-resistant microorganisms.

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