Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases.

The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. By contrast to vaborbactam and enmetazobactam, taniborbactam, xeruborbactam, and all diazabicyclooctanes demonstrated effective activities against most AmpC enzymes. Notably, durlobactam exhibited the most pronounced inhibitory effect.

Occurrence of beta-lactamases in bacteria.

Our study highlights the escalating issue of beta-lactam resistance in nosocomial pathogens, driven by the broad spectrum of antibiotic-degrading enzymes and plasmid exchange. We catalogued known beta-lactamases across 230 bacterial genera, identified 2349 potential beta-lactamases across over 673 genera, and anticipate discovering many new types, underscoring the need for targeted gene analysis in combating resistance. This study also elucidates the complex relationship between the diversity and frequency of beta-lactamase genes across bacterial genera, highlighting the need for genus-specific approaches in combating antibiotic resistance and emphasizing these genes' significant global distribution and host-specific prevalence.

Analysis of BlaEC family class C beta-lactamase.

Recent years have witnessed an increased prevalence of intrinsic and acquired beta-lactamase-producing bacteria, severely limiting human and veterinary medicine therapeutic options. The present study aimed to design specific oligonucleotides for rapid PCR detection of the cephalosporinase-encoding gene blaEC (BlaEC family class C beta-lactamase). A total of three primers were designed to detect 2281 variants of the blaEC gene and two sets of primer pairs were also tested against DNA from 11 strains.

Analysis of Bacterial Pathogens Causing Complicating HAP in Patients with Secondary Peritonitis.

Background: Diffuse peritonitis is an acute abdominal condition characterized by high mortality. The main treatment modality is surgery, requiring a subsequent prolonged hospital stay. These patients are, among other things, at risk of developing hospital-acquired pneumonia (HAP), which considerably worsens their treatment outcomes.

Insights into the Resistome and Phylogenomics of a ST195 Multidrug-Resistant Clinical Isolate from the Czech Republic.

Increasing antimicrobial resistance in nosocomial pathogens, such as , is becoming a serious threat to public health. It is necessary to detect -lactamase-producing microorganisms in clinical settings to be able to control the spread of carbapenem resistance. This study was conducted to evaluate the presence of -lactamases in a selected clinical isolate of of ST2/ST195 and to characterize possible enzymes, as well as its -lactam resistome, using PCR and whole-genome sequencing analysis.

In Silico Analysis of Extended-Spectrum β-Lactamases in Bacteria.

The growing bacterial resistance to available β-lactam antibiotics is a very serious public health problem, especially due to the production of a wide range of β-lactamases. At present, clinically important bacteria are increasingly acquiring new elements of resistance to carbapenems and polymyxins, including extended-spectrum β-lactamases (ESBLs), carbapenemases and phosphoethanolamine transferases of the MCR type. These bacterial enzymes limit therapeutic options in human and veterinary medicine.

Detection of clinically important β-lactamases by using PCR.

Increasing antimicrobial resistance of nosocomial pathogens is becoming a serious threat to public health. To control the spread of this resistance, it is necessary to detect β-lactamase-producing organisms in the clinical setting. The aims of the study were to design a PCR assay for rapid detection of clinically encountered β-lactamase genes described in Enterobacteriaceae and Gram-negative non-fermenting bacteria.

Implementation of Antibiotic Stewardship in a University Hospital Setting.

The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of , , and to selected antibiotic agents as well as consumption data for various antibiotic classes. The genetic basis of resistance to beta-lactam antibiotics and its clonal spread were also assessed.

Antibiotic Resistance in Nosocomial Bacteria Isolated from Infected Wounds of Hospitalized Patients in Czech Republic.

Hospitalized patients with wounds face an increased risk of infection with multi-drug-resistant nosocomial bacteria. In this study, samples from almost 10,000 patients from big hospitals in Czech Republic with infected wounds were analyzed for the presence of bacterial pathogens. In 7693 patients (78.

PCR Detection of Oxacillinases in Bacteria.

Oxacillinases (OXA) have been mostly described in Enterobacteriaceae, , and species. Recent years have witnessed an increased prevalence of intrinsic and/or acquired β-lactamase-producing in food-producing animals. This study was conducted to assess the prevalence of OXA among selected bacterial species and to characterize these enzymes by analysis.

Occurrence and Antibiotic Resistance of Enterobacteriaceae in Acute Leukemia Patients.

Background: Acute leukemia (AL) is a heterogeneous group of malignant hematopoietic diseases and is divided into two basic types: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Patients with these diseases are highly immunosuppressed and therefore at a high risk of serious infections. This study aimed to perform active surveillance of enterobacteria, which cause these infections, and to determine their antibiotic resistance in patients with AL who were hospitalized at the Hemato-Oncology Center of University Hospital Olomouc.

Molecular mechanisms of polymyxin resistance and detection of mcr genes.

Antibiotic resistance is an ever-increasing global problem. Major commercial antibiotics often fail to fight common bacteria, and some pathogens have become multi-resistant. Polymyxins are potent bactericidal antibiotics against gram-negative bacteria.

Molecular evidence of infection with air sac nematodes in the great tit (Parus major) and the captive-bred gyrfalcon (Falco rusticolus).

Serratospiculiasis is a parasitic disease caused by filariid nematodes of the genus Serratospiculum that parasitise the air sacs of various species of falcons, bald eagles and Cooper's hawks around the world. An infection with Serratospiculum was recently confirmed in a nonspecific host, the great tit, in Slovakia. Parasitic material from this host was fixed for molecular analysis.

Identification of novel OXA-134-like β-lactamases in Acinetobacter lwoffii and Acinetobacter schindleri isolated from chicken litter.

Background: Various food-producing animals have been recognized in recent years as a potential reservoir for the spread of antibiotic resistant bacteria that may pose a risk to human health and therefore their dissemination in the food production chain needs to be assessed.

Methods: In this study, 450 boot swabs from chicken farms were analyzed for the presence of antimicrobial resistance with a focus on β-lactams resistance in Acinetobacter species.

Results: Two β-lactamase-encoding genes were first time identified in Acinetobacter lwoffii and Acinetobacter schindleri isolates.

Antibiotic Susceptibility of spp. Isolated from Clinical Samples.

spp. have been recognized as causative agents of various severe infections in pre-term or full-term infants as well as elderly adults suffering from serious underlying disease or malignancy. A surveillance study was designed to identify antibiotic resistance among clinical spp.

Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa.

Background: Planktonic stationary and exponential cultures of Pseudomonas aeruginosa are highly resistant to killing by bactericidal antimicrobials because of the presence of persisters, cells that are multidrug tolerant and play a key role in the recalcitrance of biofilm infections.

Aim: The aim of this study was to investigate the formation of persister cells in P. aeruginosa stationary vs.

Polymyxin: Alternative Mechanisms of Action and Resistance.

Antibiotic resistance among pathogenic bacteria is an ever-increasing issue worldwide. Unfortunately, very little has been achieved in the pharmaceutical industry to combat this problem. This has led researchers and the medical field to revisit past drugs that were deemed too toxic for clinical use.

Primer Evaluation for PCR and its Application for Detection of Carbapenemases in Enterobacteriaceae.

Background: During the last decade, the prevalence of carbapenem-resistant Enterobacteriaceae in human patients has increased. Carbapenemase-producing bacteria are usually multidrug resistant. Therefore, early recognition of carbapenemase producers is critical to prevent their spread.

Exploitation of complement regulatory proteins by Borrelia and Francisella.

Pathogens have developed sophisticated mechanisms of complement evasion such as binding to the host complement regulatory proteins (CRPs) on their surface or expression of CRP mimicking molecules. The ability of pathogens to evade the complement system has been correlated with pathogenesis and host selectivity. Hitherto, little work has been undertaken to determine whether Borrelia and Francisella exploit various CRPs to block complement attack.

Deciphering the protein interaction in adhesion of Francisella tularensis subsp. holarctica to the endothelial cells.

Extracellular form of Francisella is able to cross various cell barriers and invade multiple organs, such as skin, liver, lung and central nervous system. Transient adhesion of Francisella to endothelial cells may trigger the process of translocation. In this report, we showed that Francisella tularensis subsp.

[New technologies for antibiotic susceptibility testing of bacteria].

The past two decades have witnessed increasing infections due to multidrug-resistant bacteria. Therefore, transmission of these pathogens could limit the antibiotic therapy options. Many reports suggest that initiation of appropriate antimicrobial therapy can be lifesaving.

Deciphering the interface between a CD40 receptor and borrelial ligand OspA.

Neuroborreliosis is serious sequelae of Lyme borreliosis. Neuroinvasion is largely relied on successful translocation of Borrelia across the blood-brain barrier. Adherence of Borrelia to brain microvascular endothelial cell (BMEC) seems to be critical for translocation.

Variable regions in the sushi domains 6-7 and 19-20 of factor H in animals and human lead to change in the affinity to factor H binding protein of Borrelia.

Borrelia binds host's complement regulatory factor H (fH) to evade complement attack. However, binding affinities between fH-binding-proteins (FHBPs) of Borrelia and fH from various hosts are disparate. Experiments performed to unfold the underlying molecular basis of this disparity revealed that recombinant BbCRASP-1 (major FHBP of Borrelia burgdorferi) neither interacted with sushi 6-7, nor with sushi 19-20 domains of fH in cattle and pig, however, showed binding affinity to both sushi domains of human fH, sushi 6-7 of mouse and sushi 19-20 of sheep.

Development of simple and rapid elution methods for proteins from various affinity beads for their direct MALDI-TOF downstream application.

Commercially available desalting techniques, necessary for downstream MALDI-TOF analysis of proteins, are often costly or time consuming for large-scale analysis. Here, we present techniques to elute proteins from various affinity resins, free from salt and ready for MALDI mass spectrometry. We showed that 0.

OspA-CD40 dyad: ligand-receptor interaction in the translocation of neuroinvasive Borrelia across the blood-brain barrier.

Lyme borreliosis is the most widespread vector-borne disease in temperate zones of Europe and North America. Although the infection is treatable, the symptoms are often overlooked resulting in infection of the neuronal system. In this work we uncover the underlying molecular mechanism of borrelial translocation across the blood-brain barrier (BBB).