scholarly journals Historical Review of the Penicillin and Related Compounds (β – Lactams)

2018 ◽  
pp. 109-127
Keyword(s):  
Antibiotic Resistance ◽  
Therapeutic Agent ◽  
Historical Review ◽  
Clinical Effectiveness ◽  
Good Health ◽  
Beta Lactam ◽  
Present Survey ◽  
Beta Lactam Antibiotics ◽  
Lactam Ring ◽  
Related Compounds

In spite of the old age of beta lactam, they continue to provide good health and preventing human diseases by virtue of industrial production and discoveries of small new beta-lactam group of secondary metabolites. Antibiotic resistance in bacteria has become a serious problem worldwide therefore, the present survey discusses the event that occurred in the progress of the penicillin, and beta-lactam from discovery to implementation as a therapeutic agent in order to overcome this issue. Moreover, this review provides a descriptive overview of the various published ways to enhance the clinical effectiveness of beta-lactam antibiotics and the methods that lead to synthesis of beta-lactam ring.

scholarly journals Growing Menace of Antibacterial Resistance in Clinical Isolates ofPseudomonas aeruginosain Nepal: An Insight of Beta-Lactamase Production

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shamshul Ansari ◽  
Rabindra Dhital ◽  
Sony Shrestha ◽  
Sangita Thapa ◽  
Ram Puri ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Opportunistic Pathogen ◽  
Resistance Rate ◽  
Diffusion Method ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Microbiological Methods ◽  
Immunosuppressed Patients

Introduction. Pseudomonas aeruginosais the most frequently isolated organism as it acts as the opportunistic pathogen and can cause infections in immunosuppressed patients. The production of different types of beta-lactamases renders this organism resistant to many commonly used antimicrobials. Therefore, the aim of this study was to document the antibiotic resistance rate inPseudomonas aeruginosaisolated from different clinical specimens.Methods. Pseudomonas aeruginosarecovered was identified by standard microbiological methods. Antibiotic susceptibility testing was performed by modified Kirby-Bauer disc diffusion method following Clinical and Laboratory Standard Institute (CLSI) guidelines and all the suspected isolates were tested for the production of ESBLs, MBLs, and AmpC.Results.Out of total (178) isolates, 83.1% were recovered from the inpatient department (IPD). Majority of the isolates mediated resistance towards the beta-lactam antibiotics, while nearly half of the isolates were resistant to ciprofloxacin. Most of the aminoglycosides used showed resistance rate up to 75% but amikacin proved to be better option. No resistance to polymyxin was observed. ESBLs, MBLs, and AmpC mediated resistance was seen in 33.1%, 30.9%, and 15.7% isolates, respectively.Conclusions. Antibiotic resistance rate and beta-lactamase mediated resistance were high. Thus, regular surveillance of drug resistance is of utmost importance.

scholarly journals Full-Genome Sequencing Identifies in the Genetic Background Several Determinants That Modulate the Resistance Phenotype in Methicillin-Resistant Staphylococcus aureus Strains Carrying the Novel mecC Gene

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Catarina Milheiriço ◽  
Hermínia de Lencastre ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Genetic Background ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistance Phenotype ◽  
Beta Lactam Antibiotics ◽  
Oxacillin Resistance ◽  
Mrsa Strains

ABSTRACT Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant—the mecC gene—was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecC determinant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant.

scholarly journals Evaluation of the presence of AmpC (FOX) beta-lactamase gene in clinical strains of Escherichia coli isolated from hospitalized patients in Tabriz, Iran

2021 ◽  
Vol 38 (3) ◽  
pp. 301-304
Author(s):  
Zahra SADEGHI DEYLAMDEH ◽  
Abolfazl JAFARI SALES
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Hospitalized Patients ◽  
Disk Diffusion ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Clinical Strains ◽  
Beta Lactam Antibiotics ◽  
Lactamase Gene

Beta-lactamases are the most common cause of bacterial resistance to beta-lactam antibiotics. AmpC-type beta-lactamases hydrolyze cephalosporins, penicillins, and cephamycins. Therefore, the study aims was to determine antibiotic resistance and to investigate the presence of AmpC beta-lactamase gene in clinical strains of Escherichia coli isolated from hospitalized patients in Tabriz. In this cross-sectional descriptive study, 289 E. coli specimens were collected from clinical specimens. Disk diffusion method and combined disk method were used to determine the phenotype of extended spectrum β-Lactamase producing (ESBLs) strains. Then PCR was used to evaluate the presence of AmpC (FOX) beta-lactamase gene in the strains confirmed in phenotypic tests. Antibiotic resistance was also determined using disk diffusion by the Kibry-Bauer method. A total of 121 isolates were identified as generators of beta-lactamase genes. 72 (59.5 %) isolates producing ESBL and 49 (40.5 %) isolates were identified as AmpC generators. In the PCR test, 31 isolates contained the FOX gene. The highest resistance was related to the antibiotics amoxicillin (76.12%), ceftazidime (70.24%) and nalidixic acid (65.05%). The results indicate an increase in the prevalence of beta-lactamase genes and increased resistance to beta-lactam antibiotics, which can be the result of improper use of antibiotics and not using antibiotic susceptibility tests before starting treatment. Also, using phenotypic and molecular diagnostic methods such as PCR together can be very useful.

scholarly journals Appearance of synthetic vector-associated antibiotic resistance genes in next-generation sequences

2018 ◽  
Author(s):  
George Taiaroa ◽  
Gregory M. Cook ◽  
Deborah A Williamson
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Sequence Data ◽  
Antibiotic Resistance Genes ◽  
Data Sets ◽  
Next Generation ◽  
Beta Lactam ◽  
Sequence Contigs ◽  
Beta Lactam Antibiotics ◽  
Genome Shotgun Sequence

SynopsisBackgroundNext-generation sequencing methods have broad application in addressing increasing antibiotic resistance, with identification of antibiotic resistance genes (ARGs) having direct clinical relevance.ObjectivesHere, we describe the appearance of synthetic vector-associated ARGs in major public next-generation sequence data sets and assemblies, including in environmental samples and high priority pathogenic microorganisms.MethodsA search of selected databases – the National Centre for Biotechnology Information (NCBI) nucleotide collection, NCBI whole genome shotgun sequence contigs and literature-associated European Nucleotide Archive (ENA) datasets, was carried out using sequences characteristic of pUC-family synthetic vectors as a query in BLASTn. Identified hits were confirmed as being of synthetic origin, and further explored through alignment and comparison to primary read sets.ResultsSynthetic vectors are attributed to a range of organisms in each of the NCBI databases searched, including examples belonging to each Kingdom of life. These synthetic vectors are associated with various ARGs, primarily those encoding resistance to beta-lactam antibiotics and aminoglycosides. Synthetic vector associated ARGs are also observed in multiple environmental meta-transcriptome datasets, as shown through analysis of associated ENA primary reads, and are proposed to have led to incorrect statements being made in the literature on the abundance of ARGs.ConclusionsAppearance of synthetic vector-associated ARGs can confound the study of antimicrobial resistance in varied settings, and may have clinical implications in the nearfuture.

scholarly journals The Raw Milk Microbiota from Semi-Subsistence Farms Characteristics by NGS Analysis Method

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5029
Author(s):  
Bartosz Hornik ◽  
Jakub Czarny ◽  
Justyna Staninska-Pięta ◽  
Łukasz Wolko ◽  
Paweł Cyplik ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Resistance ◽  
16S Rrna Gene Sequencing ◽  
Raw Milk ◽  
Microbial Consortia ◽  
Bacterial Metabolism ◽  
Rrna Gene ◽  
Environmental Niche ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics

The aim of this study was to analyze the microbiome of raw milk obtained from three semi-subsistence farms (A, B, and C) located in the Kuyavian-Pomeranian Voivodeship in Poland. The composition of drinking milk was assessed on the basis of 16S rRNA gene sequencing using the Ion Torrent platform. Based on the conducted research, significant changes in the composition of the milk microbiome were found depending on its place of origin. Bacteria belonging to the Bacillus (17.0%), Corynebacterium (12.0%) and Escherichia-Shigella (11.0%) genera were dominant in the milk collected from farm A. In the case of the milk from farm B, the dominant bacteria belonged to the Acinetobacter genus (21.0%), whereas in the sample from farm C, Escherichia-Shigella (24.8%) and Bacillus (10.3%) dominated the microbiome. An analysis was performed using the PICRUSt tool (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) in order to generate a profile of genes responsible for bacterial metabolism. The conducted analysis confirmed the diversity of the profile of genes responsible for bacterial metabolism in all the tested samples. On the other hand, simultaneous analysis of six KEGG Orthologs (KO), which participated in beta-lactam resistance responsible for antibiotic resistance of bacteria, demonstrated that there is no significant relationship between the predicted occurrence of these orthologs and the place of existence of microorganisms. Therefore, it can be supposed that bacterial resistance to beta-lactam antibiotics occurs regardless of the environmental niche, and that the antibiotic resistance maintained in the population is a factor that shapes the functional structure of the microbial consortia.

scholarly journals Analysis of bacterial cell-wall synthesis to combat antibiotic resistance

2014 ◽  
Vol 70 (a1) ◽  
pp. C701-C701
Author(s):  
Dustin King ◽  
Natalie Strynadka
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Bacterial Cell ◽  
Kinetic Properties ◽  
Enzymatic Reactions ◽  
Beta Lactam ◽  
Antimicrobial Drugs ◽  
Beta Lactam Antibiotics ◽  
Major Structural Component ◽  
Lactam Antibiotic

The peptidoglycan biosynthetic pathway is one of the most important processes in the bacterial cell to be exploited as a target for the design of antimicrobial drugs to combat infection and pathogenesis. This pathway, unique to bacteria, utilizes over twenty enzymes, likely in concert, with reactions that proceed from the cytoplasm, across the membrane and into the periplasmic space culminating in the production of the mesh-like structure composed of polymerized glycan and cross-linked peptide components that form the major structural component of the essential bacterial protective barrier known as the cell wall. Work in our group has aimed at understanding the structural and kinetic properties of several of these enzymes including the glycosyltransferase/transpeptidase activity of a family of enzymes known historically as the penicillin binding proteins (PBPs). As the name implies, these enzymes are also the target of beta-lactam antibiotics, and molecular modifications to transpeptidase variants have been shown to be linked to increased antibiotic resistance in superbugs such as Methicillin Resistant Staphlococcal aureus (MRSA). In parallel, highly disseminated plasmid-encoded beta-lactamase enzymes, with structural and mechanistic ties to the transpeptidases, have also arisen in many of the clinically important bacterial pathogens, leading to further widespread beta-lactam antibiotic resistance. The molecular details of these critical enzymatic reactions in bacterial viability and drug resistance will be presented.

scholarly journals Monitoring of gram-negative bacteria and antibiotic resistance in osteomyelitis

2020 ◽  
Vol 26 (4) ◽  
pp. 544-547
Author(s):  
I.V. Shipitsyna ◽  
◽  
E.V Osipova ◽  
D.S. Leonchuk ◽  
A.S. Sudnitsyn ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Regular Monitoring ◽  
Beta Lactam Antibiotics ◽  
Bacterial Morphology ◽  
Acinetobacter Sp ◽  
Drug Resistant Strains

Introduction There is an urgent need for a surveillance system of regular monitoring of specific bacteria inducing various types of osteomyelitis to identify resistant isolates and optimize the use of antibiotics. Objective: monitoring of specific gram-negative bacteria and analysis of the antibiotic resistance of the strains isolated from osteomyelitis patients over a three-year period. Results and discussion P. aeruginosa was the first most common pathogen among gram-negative microorganisms isolated from the patients between 2017 and 2019. Prevalence of the isolates identified in 2019 decreased by 9.6 % as compared to 2017. Next frequently encountered clinical isolates were Enterobacter sp., Acinetobacter sp., Klebsiella sp. There was a twofold increase in K. pneumoniae strains isolated in 2019. Analysis of antibiotic susceptibility testing data revealed multiresistance of the Acinetobacter sp. strains in 2019 despite the total decrease in resistant isolates in 2017 and 2018. Among non-fermenting gram-negative rods, the species being resistant to imipenem were shown to increase by 5.4 times. Overall antibiotic resistance was on rise. Increased antimicrobial resistance to beta-lactam antibiotics also combined with BLaC inhibitors was observed in Enterobacteriaceae population. Meropenem was found to be effective against most bacteria with growing drug resistance observed as compared with recent years. The antibiotic resistance profiles of Klebsiella sp. strains appeared to be high at antimicrobial testing. Conclusion Diverse bacterial morphology of gram-negative species and increasing proportion of drug-resistant strains isolated in osteomyelitis cases have necessitated regular monitoring of multiresistant clinical isolates for adjustment of empirical antibiotic therapies.

scholarly journals Redox protein OsaR (PA0056) regulates dsbM and the oxidative stress response in Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Yujie Liu ◽  
Yibing Ma ◽  
Zhongqiang Ma ◽  
Xiao Han ◽  
Hang Qi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Stress Response ◽  
Gene Cluster ◽  
Oxidative Stress Response ◽  
Antibiotics Resistance ◽  
Transcriptional Level ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics

Bacteria have evolved distinct molecular mechanisms as a defense against oxidative stress. The foremost regulator of oxidative stress response has been found to be OxyR. However, the molecular details of regulation upstream of OxyR remain largely unknown and need further investigation. Here, we characterize a oxidant stress and antibiotic tolerance regulator, OsaR (PA0056), produced by Pseudomonas aeruginosa. Mutation of osaR increased bacterial tolerance to aminoglycoside and beta-lactam antibiotics, as well as to hydrogen peroxide. Expression of the oxyR regulon genes oxyR, katAB, and ahpBCF was increased in the osaR mutant. However, the OsaR protein does not regulate the oxyR regulon genes through direct binding to their promoters. PA0055, osaR, PA0057 and dsbM are in the same gene cluster, and we provide evidence that expression of these genes involved in oxidant tolerance is controlled by binding of OsaR to intergenic region between osaR and PA0057, which contain two divergent promoters. The gene cluster is also regulated by PA0055 via an indirect effect. We further discovered that OsaR formed intramolecular disulfide bonds when exposed to oxidative stress, resulting in a change of its DNA binding affinity. Taken together, our results indicate that OsaR is inactivated by oxidative stress and plays a role in the tolerance of P. aeruginosa to aminoglycoside and beta-lactam antibiotics. IMPORTANCE As opportunistic pathogen, Pseudomonas aeruginosa can cause serious infections which are hard to eradicate because of antibiotic resistance in immunodeficient patients. We found that OsaR is involved in oxidative stress and antibiotics resistance by regulation of downstream genes via redox state change. Research on factors affecting the transcriptional level of oxyR is very limited, but important since it has implications on antibiotic resistance. In this study, it was found that OsaR can indirectly inhibit transcription of oxyR. In addition the gene cluster composed of PA0055, osaR, PA0057 and dsbM was identified, and the associated regulatory mechanisms and functions were elucidated. Our work not only provides a mechanistic understanding of antibiotic tolerance regulation in P. aeruginosa, but also has significant implications for redox regulation in human pathogens in general.

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