Low-level Resistance Research Articles

Characteristics of the components of psycho-emotional stability of high school students in the process of physical education

The article examines the subjective characteristics of the psycho-emotional state of high school students using psychological questionnaires. So, in general, 45.0% of students have a high level of well-being, activity - 35.0% of schoolchildren, mood - 25.0% of student youth. It was found that the resistance to stress in extreme situations of the vast majority of high school age boys is in the range from below average to average levels. The study of anxiety showed that, in general, high school students have a slightly increased level of reactive (situational) and personal anxiety (45.4±9.7 points and 44.1±10.1 points, respectively, at p<0.05). According to the results of the assessment of willpower, it was established that this indicator of willpower in high school students is on average 18.1±4.5 points and corresponds to the average level. As for determination, on average, 52.5% of the studied 10-11 graders can be called determined. The results of determining the level of stress made it possible to establish a certain single trend at this age, namely: a low level of resistance to stress is characteristic of 12.01% of the examinees, an average level - 59.42%, and a high level - 28.57%.

Recent dynamics in Neisseria gonorrhoeae genomic epidemiology in Brazil: antimicrobial resistance and genomic lineages in 2017-20 compared to 2015-16.

Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology. WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined. Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015-16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1-A4, while isolates within lineage B remained diverse in Brazil. Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries.

Mutations in the efflux pump regulator MexZ shift tissue colonization by Pseudomonas aeruginosa to a state of antibiotic tolerance

Mutations in mexZ, encoding a negative regulator of the expression of the mexXY efflux pump genes, are frequently acquired by Pseudomonas aeruginosa at early stages of lung infection. Although traditionally related to resistance to the first-line drug tobramycin, mexZ mutations are associated with low-level aminoglycoside resistance when determined in the laboratory, suggesting that their selection during infection may not be necessarily, or only, related to tobramycin therapy. Here, we show that mexZ-mutated bacteria tend to accumulate inside the epithelial barrier of a human airway infection model, thus colonising the epithelium while being protected against diverse antibiotics. This phenotype is mediated by overexpression of lecA, a quorum sensing-controlled gene, encoding a lectin involved in P. aeruginosa tissue invasiveness. We find that lecA overexpression is caused by a disrupted equilibrium between the overproduced MexXY and another efflux pump, MexAB, which extrudes quorum sensing signals. Our results indicate that mexZ mutations affect the expression of quorum sensing-regulated pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within patients, something unnoticeable using standard laboratory tests.

Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125-1 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae strains in a hollow fibre infection model for gonorrhoea.

Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125-1 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC > 0.125 mg/L), in our hollow fibre infection model (HFIM) for gonorrhoea. Gonococcal strains examined were WHO F (ceftriaxone-susceptible, MIC < 0.002 mg/L), R (ceftriaxone-resistant, MIC = 0.5 mg/L), Z (ceftriaxone-resistant, MIC = 0.5 mg/L) and X (ceftriaxone-resistant, MIC = 2 mg/L). Dose-range HFIM 7 day experiments simulating ceftriaxone 0.125-1 g single-dose intramuscular regimens were conducted. Ceftriaxone 0.125-1 g single-dose treatments rapidly eradicated WHO F (wild-type ceftriaxone MIC). Ceftriaxone 0.5 and 1 g treatments, based on ceftriaxone human plasma pharmacokinetic parameters, eradicated most ceftriaxone-resistant gonococcal strains (WHO R and Z), but ceftriaxone 0.5 g failed to eradicate WHO X (high-level ceftriaxone resistance). When simulating oropharyngeal gonorrhoea, ceftriaxone 0.5 g failed to eradicate all the ceftriaxone-resistant strains, while ceftriaxone 1 g eradicated WHO R and Z (low-level ceftriaxone resistance) but failed to eradicate WHO X (high-level ceftriaxone resistance). No ceftriaxone-resistant mutants were selected using any ceftriaxone treatments. Ceftriaxone 1 g single-dose intramuscularly cure most of the anogenital and oropharyngeal gonorrhoea cases caused by the currently internationally spreading ceftriaxone-resistant gonococcal strains, which should be further confirmed clinically. A ceftriaxone 1 g dose (±azithromycin 2 g) should be recommended for first-line empiric gonorrhoea treatment. This will buy countries some time until novel antimicrobials are licensed. Using ceftriaxone 1 g gonorrhoea treatment, the EUCAST ceftriaxone-resistance breakpoint is too low.

Mutation in PgABCC2 confers low-level resistance to Cry1Ac in pink bollworm.

With the increasing incidence of pest resistance to transgenic crops producing Bacillus thuringiensis (Bt) proteins in the field, elucidating the molecular basis of resistance is important for monitoring, delaying and countering pest resistance. Previous work revealed that mutation or down-regulated expression of the cadherin gene (PgCad1) is associated with pink bollworm (Pectinophora gossypiella) resistance to Cry1Ac, and 20 mutant PgCad1 alleles (r1-r20) were characterized. Here, we tested the hypothesis that the ABC transporter PgABCC2 is a functional receptor for the Bt toxin Cry1Ac and that a mutation is associated with resistance. We identified and characterized the first resistance allele (rC2) of PgABCC2 in the laboratory-selected Cry1Ac-resistant strain AQ-C2 of pink bollworm. The rC2 allele had a one-base deletion in exon20, resulting in a frameshift and the introduction of a premature stop codon. This resulting PgABCC2 protein had a truncated C-terminus, including the loss of the NBD2 domain. AQ-C2 exhibited 20.2-fold greater resistance to Cry1Ac than the susceptible strain, and its inheritance of Cry1Ac resistance was recessive and genetically linked to PgABCC2. When produced in cultured insect cells, recombinant wild-type and rC2 mutant PgABCC2 proteins localized within the cell plasma membrane, although substantial cytoplasmic retention was also observed for the mutant protein, while the mutant PgABCC2 caused a 13.9-fold decrease in Cry1Ac toxicity versus the wild-type PgABCC2. PgABCC2 is a functional receptor of Cry1Ac and the loss of its carboxyl terminus (including its NBD2 domain) confers low-level resistance to Cry1Ac in both larvae and in cultured cells. © 2024 Society of Chemical Industry.

Ciprofloxacin and Azithromycin Susceptibility in Salmonella Causing Bloodstream Infection in a Tertiary Care Hospital in South India

Enteric fever is a major health concern worldwide, especially in tropical countries. Enteric fever caused by Salmonella enterica is a gastrointestinal tract disease to begin with and later involving many systems,. After the advent of multidrug resistant Salmonellae, ciprofloxacin became the focus of its treatment. Azithromycin is widely being used for the prevention and treatment of Enteric fever. Of late, there are reports in literature to support that Salmonella have regained susceptibility to Ampicillin, Cotrimaxazole and Chloramphenicol. Therefore, this study undertaken aims to find out the antimicrobial susceptibility of Salmonella isolates to conventional drugs like Ampicillin, Cotrimaxazole and Chloramphenicol and find out susceptibility pattern of Ciprofloxacin that is over used for treatment of enteric fever and Azithromycin, most often used in children. As there is no disc diffusion method as per CLSI 2019 guidelines to detect the susceptibility to ciprofloxacin, ciprofloxacin resistance was determined by minimum inhibitory concentration(MIC)by E-test.Kirby-Bauer disk diffusion technique was used to monitor Azithromycin resistance among Salmonella entericaserovarTyphi as per CLSI 2019 guidelines. METHODS:The Prospective study was conducted over a period of 8 months (May 2019- December 2019) with the clinical samples yielding the growth of Salmonella from blood. These strains were screened for Ciprofloxacin susceptibility by E-test. Azithromycin,Ampicillin, Co-Trimaxazole and Chloramphenicol susceptibility were detected by Kirby-Bauer disc diffusion technique. RESULTS: Of the 80 isolates that were screened, 52 (65%) were resistant, 24 (30%) were intermediate susceptible and remaining 4(5%) were sensitive to ciprofloxacin by MIC detection. 69 (86.25%) of the isolates were sensitive and 11 (13.75%) were resistant to Azithromycin by disc diffusion technique. All isolates (100%)were found to be susceptible to Ampicillin, Co-Trimaxazole and Chloramphenicol CONCLUSION:The current study shows a high prevalence of resistance to ciprofloxacin in Salmonella species isolated in and around Mysuru district in southern India. Detection of ciprofloxacin resistance by the Kirby Bauer disk diffusion method is less effective, so it is advised that MIC of ciprofloxacin must be regularly done in the diagnostic laboratories for all strains. The findings from our study also showed low level resistance (13.75%) to Azithromycin. It is advised that Azithromycin can be used as a therapeutic agent only if it is reported to be sensitive by the susceptibility test. Conventional agents like Ampicillin, Co-Trimaxazole and Chloramphenicol can be reconsidered for treatment of Enteric fever.

Antimicrobial Resistance Profile of Group B Streptococci Colonization in a Sample Population of Pregnant Women from Romania.

Group B Streptococcus (GBS) represents one of the leading causes of life-threatening invasive disease in pregnant women and neonates. Rates of GBS colonization vary by region, but studies on maternal GBS status are limited in Romania. This study aims to identify the prevalence of colonization with GBS and whether the obstetrical characteristics are statistically associated with the study group's antimicrobial susceptibility patterns of tested GBS strains. This observational study was conducted between 1 May and 31 December 2021 at The Department of Obstetrics and Gynecology at Elias University Emergency Hospital (EUEH) in Bucharest, Romania. A total of 152 samples were positive for GBS and included in the study according to the inclusion criteria. As a result, the prevalence of colonized patients with GBS was 17.3%. GBS isolated in this population had the highest resistance to erythromycin (n = 38; 25%), followed by clindamycin (n = 36; 23.7%). Regarding the susceptibility patterns of tested strains to penicillin, the 152 susceptible strains had MIC breakpoints less than 0.06 μg/μL. The susceptibility patterns of tested strains to linezolid indicated three resistant strains with low levels of resistance (MICs ranging between 2 and 3 μg/μL). Multidrug resistance (at least three antibiotic classes) was not observed. In conclusion, although GBS naturally displays sensitivity to penicillin, the exact bacterial susceptibility testing should be performed in all cases where second-line therapy is taken into consideration for treatment. We acknowledge the need for future actions to limit multidrug-resistant bacteria.

KPC-2 allelic variants in Klebsiella pneumoniae isolates resistant to ceftazidime-avibactam from Argentina: blaKPC-80, blaKPC-81, blaKPC-96 and blaKPC-97.

The emergence of ceftazidime-avibactam (CZA) resistance poses a significant threat to the efficacy of this life-saving therapy against carbapenem-resistant bacteria, particularly Klebsiella pneumoniae-producing KPC enzymes. This study investigates four clinical isolates exhibiting resistance to CZA, revealing novel allelic variants of the key resistance gene, blaKPC-2. The mutations identified in hotspots surrounding the active site of KPC, such as K269_D270insPNK, del_I173, Y241N and V277_I278insNSEAV, prove the adaptability of these pathogens. Intriguingly, low-level resistance to imipenem and disruptions in porin genes were observed, emphasizing the complexity of the resistance mechanisms. Interestingly, three of four isolates belonged to clonal complex 11. This research not only sheds light on the clinical significance of CZA resistance but also shows the urgency for comprehensive surveillance and molecular studies to inform effective antimicrobial treatment strategies in the face of evolving bacterial resistance.

Evaluation of mechanical transmission of Enterococcus spp., resistant to antibiotics, having flies as vectors of dissemination

The objective of this work was to evaluate the mechanical transmission of Enterococcus spp., resistant to antibiotics, using flies as dissemination vectors. In this work, 50 flies were captured, 25 in “La Llanada” community, in Cumaná and 25 others in the surroundings of the “Juan Otaola Rogliani” outpatient clinic and the central cemetery of Carúpano. The main families of flies captured in the state of Sucre were Muscidae, Calliphoridae and Sarcophagidae. The flies captured in Cumaná had fewer strains of Enterococcus spp., on the surface than those from Carúpano, while those from Cumaná were more colonized in the intestine than those from Carúpano. A total of 14 strains of Enterococcus were isolated, among which were E. faecium (6%), E. gallinarum (36%) and E. casseliflavus (58%). The susceptibility profile of E. casseliflavus strains is resistance to linezolid, tetracycline, erythromycin, rifampicin and intermediate susceptibility to fluoroquinolones; E. gallinarum strains were sensitive to rifampicin and tetracycline, and resistant to the other antibiotics. The only strain of E. faecium isolated in Carúpano, presented low level of resistance to vancomycin. It did not amplify for the glycopeptide resistance ligase genes vanA, vanB, vanD, vanE, or vanG. Antibiotypes IA and IV of E. caseliflavus were detected in both Carúpano and Cumaná.

Microbial associations for pneumonia causative agents and level of their resistance to antimicrobial drugs during a new coronavirus infection pandemic

Introduction. Bacterial coinfection and secondary bacterial infection are considered critical risk factors for the severity and mortality of SARS-CoV-2-caused pneumonia. The aim of the study was to analyze a pattern of microbial associations between K. pneumoniae and A. baumannii isolated from the lower respiratory tract discharge and sectional material (lung tissue) of patients diagnosed with pneumonia, and to compare resistance level in monoculture and associations during new coronavirus infection pandemic. Materials and methods. A bacteriological study of 2689 sputum and bronchial washing samples from patients at infectious diseases hospitals, and 1411 lung pathological material samples was carried out. Bacterial isolates were identified by mass spectrometry. Antibiotic sensitivity for isolates was determined by the disk diffusion method. Genetic determinants of resistance to beta-lactam antibiotics were detected by PCR. Statistical data processing was performed using SPSS version 22 software. Results. K. pneumoniae and A. baumannii isolates were predominantly found in two- and three-pathogen associations. It was established that the resistance level of K. pneumoniae isolates in association with A. baumannii is significantly higher compared to that in monoculture for all antimicrobial drugs studied. At the same time, K. pneumoniae in combination with Candida spp. vs monoculture showed significantly lower level of resistance to ciprofloxacin, amikacin, cefotaxime, ceftazidime and amoxicillin/clavulanic acid. K. pneumoniae isolates carried resistance determinants to extended-spectrum beta-lactamases: OXA-48 — (22.5%), OXA-51 — (5.6%), OXA-23 — (4.2%), KPC — 70.9%, NDM — 7%. Of these, 14.1% of strains had the ability to co-produce serine carbapenemases OXA-48 and KPC. Sputum and lung tissue A. baumannii isolates exhibited extremely high multiple resistance regardless of their associations with other microorganisms. Microbiome species similarity in the lower respiratory tract and lung tissue discharge was revealed. The proportion of lung tissue vs sputum resistant strains of K. pneumoniae and A. baumannii was significantly higher. Conclusion. The detection of of multiple drug resistant K. pneumoniae and A. baumannii isolates as well as their associations may indicate aggravated pneumonia severity.

Antimicrobial susceptibility pattern and mupirocin resistance among methicillin-resistant Staphylococcus aureus isolated from skin and soft-tissue infection patients attending a tertiary care hospital in North India

Background: Antimicrobial susceptibility among bacterial isolates varies from center to center. Mupirocin is a topical antibacterial antibiotic used to treat wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Aim and Objectives: This study was conducted to know the prevalence of high and low levels of mupirocin resistance along with antimicrobial susceptibility in MRSA isolates from skin and soft-tissue infection in patients admitted to a tertiary care hospital in North India. Materials and Methods: A total of 97 non-repetitive isolates of MRSA from various pus samples over a period of 1 year were included in this study. These strains were identified as per standard laboratory protocols given by the Clinical Laboratory Standards Institute. High- and low-level mupirocin resistance of the isolates was tested by using mupirocin discs of 200 μg and 5 μg, respectively. Mupirocin strips of 256 μg and 512 μg were used for the E-test to detect low-level and high-level mupirocin resistance, respectively. The isolates were reported as sensitive to mupirocin, with minimum inhibitory concentrations of &lt;4 mg/L. Results: Overall, 9.27% of mupirocin resistance was found, of which 2.06% of isolates were high-level resistant to mupirocin, while 7.21% had low-level resistance. All MRSA strains were susceptible to vancomycin, followed by linezolid (94.84%), teicoplanin (91.75%), and fusidic acid (88.65%). Conclusion: Regular monitoring, good infection control practices, and proper awareness about utilizing mupirocin therapeutically and prophylactically may help prevent the emergence of mupirocin resistance in health-care facilities.

Fitness trade-offs of multidrug efflux pumps in Escherichia coli K-12 in acid or base, and with aromatic phytochemicals.

Multidrug efflux pumps are the frontline defense mechanisms of Gram-negative bacteria, yet little is known of their relative fitness trade-offs under gut conditions such as low pH and the presence of antimicrobial food molecules. Low pH contributes to the proton-motive force (PMF) that drives most efflux pumps. We show how the PMF-dependent pumps AcrAB-TolC, MdtEF-TolC, and EmrAB-TolC undergo selection at low pH and in the presence of membrane-permeant phytochemicals. Competition assays were performed by flow cytometry of co-cultured Escherichia coli K-12 strains possessing or lacking a given pump complex. All three pumps showed negative selection under conditions that deplete PMF (pH 5.5 with carbonyl cyanide 3-chlorophenylhydrazone or at pH 8.0). At pH 5.5, selection against AcrAB-TolC was increased by aromatic acids, alcohols, and related phytochemicals such as methyl salicylate. The degree of fitness cost for AcrA was correlated with the phytochemical's lipophilicity (logP). Methyl salicylate and salicylamide selected strongly against AcrA, without genetic induction of drug resistance regulons. MdtEF-TolC and EmrAB-TolC each had a fitness cost at pH 5.5, but salicylate or benzoate made the fitness contribution positive. Pump fitness effects were not explained by gene expression (measured by digital PCR). Between pH 5.5 and 8.0, acrA and emrA were upregulated in the log phase, whereas mdtE expression was upregulated in the transition-to-stationary phase and at pH 5.5 in the log phase. Methyl salicylate did not affect pump gene expression. Our results suggest that lipophilic non-acidic molecules select against a major efflux pump without inducing antibiotic resistance regulons.IMPORTANCEFor drugs that are administered orally, we need to understand how ingested phytochemicals modulate drug resistance in our gut microbiome. Bacteria maintain low-level resistance by proton-motive force (PMF)-driven pumps that efflux many different antibiotics and cell waste products. These pumps play a key role in bacterial defense by conferring resistance to antimicrobial agents at first exposure while providing time for a pathogen to evolve resistance to higher levels of the antibiotic exposed. Nevertheless, efflux pumps confer energetic costs due to gene expression and pump energy expense. The bacterial PMF includes the transmembrane pH difference (ΔpH), which may be depleted by permeant acids and membrane disruptors. Understanding the fitness costs of efflux pumps may enable us to develop resistance breakers, that is, molecules that work together with antibiotics to potentiate their effect. Non-acidic aromatic molecules have the advantage that they avoid the Mar-dependent induction of regulons conferring other forms of drug resistance. We show that different pumps have distinct selection criteria, and we identified non-acidic aromatic molecules as promising candidates for drug resistance breakers.

Construction of ecological security pattern based on InVEST-Conefor-MCRM: A case study of Xinjiang, China

Constructing ecological security patterns (ESP) effectively maintains ecosystems' green, healthy, and sustainable development. The InVEST model and Conefor software were utilized in this study to pinpoint ecological sources (eco-sources) through a blend of landscape connectivity and the importance of ecosystem services (IES); the ecological resistance surface was constructed by synthesizing the gravity model and minimum cumulative resistance model (MCRM), extracted ecological corridors (eco-corridors) and nodes. Ultimately, the research in this study built the ESP for Xinjiang. The findings showed that: (1) 14 eco-sources were identified in Xinjiang, spanning an area of 2.13 × 105 km2; 32 eco-corridors were extracted, including 9 important and 23 general eco-corridors, comprising a total length of 1.26 × 104 km; identified 46 ecological nodes(eco-nodes); (2) the size of important and more important patches of ecosystem services in Xinjiang was 2.82 × 105 km2, which accounted for a relatively small size, and the value of ecosystem services was generally average. The overall level of landscape connectivity in the primary eco-sources was high, but the spatial distribution was uneven; (3) the ecological resistance values in Xinjiang vary significantly, with high-level resistance surfaces primarily located in the Junggar Basin and Tarim Basin and low-level resistance covering most of Xinjiang's natural ecological reserves and other areas. The study's findings can provide some references for constructing ESP at the provincial scale and in arid and semiarid regions and for planning spatial ecological restoration in Xinjiang.

Gonococcal resistance to zoliflodacin could emerge via transformation from commensal Neisseria species. An in-vitro transformation study

One of the most promising new treatments for gonorrhoea currently in phase 3 clinical trials is zoliflodacin. Studies have found very little resistance to zoliflodacin in currently circulating N. gonorrhoeae strains, and in-vitro experiments demonstrated that it is difficult to induce resistance. However, zoliflodacin resistance may emerge in commensal Neisseria spp., which could then be transferred to N. gonorrhoeae via transformation. In this study, we investigated this commensal-resistance-pathway hypothesis for zoliflodacin. To induce zoliflodacin resistance, ten wild-type susceptible isolates belonging to 5 Neisseria species were serially passaged for up to 48 h on gonococcal agar plates containing increasing zoliflodacin concentrations. Within 7 to 10 days, all strains except N. lactamica, exhibited MICs of ≥ 4 µg/mL, resulting in MIC increase ranging from 8- to 64-fold. The last passaged strains and their baseline were sequenced. We detected mutations previously reported to cause zoliflodacin resistance in GyrB (D429N and S467N), novel mutations in the quinolone resistance determining region (QRDR) (M464R and T472P) and mutations outside the QRDR at amino acid positions 28 and 29 associated with low level resistance (MIC 2 µg/mL). Genomic DNA from the laboratory evolved zoliflodacin-resistant strains was transformed into the respective baseline wild-type strain, resulting in MICs of ≥ 8 µg/mL in most cases. WGS of transformants with decreased zoliflodacin susceptibility revealed presence of the same zoliflodacin resistance determinants as observed in the donor strains. Two inter-species transformation experiments were conducted to investigate whether zoliflodacin resistance determinants of commensal Neisseria spp. could be acquired by N. gonorrhoeae. N. gonorrhoeae strain WHO P was exposed to (i) pooled genomic DNA from the two resistant N. mucosa strains and (ii) a gyrB amplicon of the resistant N. subflava strain 45/1_8. Transformants of both experiments exhibited an MIC of 2 µg/mL and whole genome analysis revealed uptake of the mutations detected in the donor strains. This is the first in-vitro study to report that zoliflodacin resistance can be induced in commensal Neisseria spp. and subsequently transformed into N. gonorrhoeae.

Structural insights into the molecular mechanism of high-level ceftazidime-avibactam resistance conferred by CMY-185.

β-Lactamases can accumulate stepwise mutations that increase their resistance profiles to the latest β-lactam agents. CMY-185 is a CMY-2-like β-lactamase and was identified in an Escherichia coli clinical strain isolated from a patient who underwent treatment with ceftazidime-avibactam. CMY-185, possessing four amino acid substitutions of A114E, Q120K, V211S, and N346Y relative to CMY-2, confers high-level ceftazidime-avibactam resistance, and accumulation of the substitutions incrementally enhances the level of resistance to this agent. However, the functional role of each substitution and their interplay in enabling ceftazidime-avibactam resistance remains unknown. Through biochemical and structural analysis, we present the molecular basis for the enhanced ceftazidime hydrolysis and impaired avibactam inhibition conferred by CMY-185. The substituted Y346 residue is a major driver of the functional evolution as it rejects primary avibactam binding due to the steric hindrance and augments oxyimino-cephalosporin hydrolysis through a drastic structural change, rotating the side chain of Y346 and then disrupting the H-10 helix structure. The other substituted residues E114 and K120 incrementally contribute to rejection of avibactam inhibition, while S211 stimulates the turnover rate of the oxyimino-cephalosporin hydrolysis. These findings indicate that the N346Y substitution is capable of simultaneously expanding the spectrum of activity against some of the latest β-lactam agents with altered bulky side chains and rejecting the binding of β-lactamase inhibitors. However, substitution of additional residues may be required for CMY enzymes to achieve enhanced affinity or turnover rate of the β-lactam agents leading to clinically relevant levels of resistance.IMPORTANCECeftazidime-avibactam has a broad spectrum of activity against multidrug-resistant Gram-negative bacteria including carbapenem-resistant Enterobacterales including strains with or without production of serine carbapenemases. After its launch, emergence of ceftazidime-avibactam-resistant strains that produce mutated β-lactamases capable of efficiently hydrolyzing ceftazidime or impairing avibactam inhibition are increasingly reported. Furthermore, cross-resistance towards cefiderocol, the latest cephalosporin in clinical use, has been observed in some instances. Here, we clearly demonstrate the functional role of the substituted residues in CMY-185, a four amino-acid variant of CMY-2 identified in a patient treated with ceftazidime-avibactam, for high-level resistance to this agent and low-level resistance to cefiderocol. These findings provide structural insights into how β-lactamases may incrementally alter their structures to escape multiple advanced β-lactam agents.

Fabrication of Sb2S3/Sb2Se3 heterostructure for potential resistive switching applications

The exponential growth of large data and the widespread adoption of the Internet of Things (IoT) have created significant challenges for traditional Von Neumann computers. These challenges include complex hardware, high energy consumption, and slow memory access time. Researchers are investigating novel materials and device architectures to address these issues by reducing energy consumption, improving performance, and enabling compact designs. A new study has successfully engineered a heterostructure that integrates Sb2Se3 and Sb2S3, resulting in improved electrical properties. This has generated significant interest in its potential applications in resistive switching. In this study, we have demonstrated the fabrication of a device based on Sb2S3/Sb2Se3 heterostructure that exhibits resistive switching behavior. The device has different resistance states that can be switched between high and low resistance levels when exposed to an external bias (−1 V to 0 V to 1 V). It also has good non-volatile memory characteristics, including low power consumption, high resistance ratio (∼102), and reliable endurance (∼103). The device enables faster data processing, reduces energy consumption, and streamlines hardware designs, contributing to computing advancements amidst modern challenges. This approach can revolutionize resistive switching devices, leading to more efficient computing solutions for big data processing and IoT technologies.

The validity and reliability of a hydraulic resistance device for assessing resisted sprint time.

The aim of this study was to assess the validity and reliability of a hydraulic resistance device (HRD) for monitoring sprint split times under different loads within and between sessions. Three 20-m sprints with low (15 N), medium-low (40 N), medium-high (50 N), and high (130 N) HRD resistance levels (loads) were performed on two separate occasions 14 days apart. Twenty-four student athletes (24.8 ± 3.8 years) participated in the first session and 13 (24.1 ± 3.2 years) of them in the second session. Resisted sprints split times over a distance of 0-20 m (t0-5, t0-10, t0-20, t5-10, t10-15, t15-20) were measured simultaneously with magnetic incremental encoder embedded in the HRD and a system of single-beam timing gates. The results showed acceptable to high within session (ICC3,1 = 0.91-0.99; CV = 0.92%-3.38%) and between session (ICC3,1 = 0.82-0.99; CV = 1.62%-4.84%) reliability of HRD for measuring all split times at all loads. The minimal detectable change between sessions ranged from 3.3% at high load to 9.9% at low load. The HRD systematically underestimated timing gates times at all loads (bias = 2.01-11.08%), yet good to excellent consistency was observed between the HRD and timing gates, specifically for t0-10 and t0-20 (ICC3,k lower 95% CI = 0.84-0.99). Due to high reliability and good validity in monitoring resisted sprint times, the HRD holds potential for practical and research applications.

Summer mortality syndrome bacterial pathogens in farmed Nile tilapia (Oreochromis niloticus).

The high summer mortality in many fish farms, which had detrimental economic and social implications, was a serious challenge that the fish industry had to deal with. With an examination of the most effective antibiotic, the ongoing research was intended to shed light on the identification of the main bacterial pathogens associated with the summer mortality syndrome in the diseased farmed Nile tilapia. Six hundred dead Nile tilapia samples that had suffered from summer mortality were collected from several fish farms between May and October of 2022. The gathered fish displayed hemorrhagic areas on the skin, scale detachment, fin degeneration, erosions, skin ulcers, and corneal opacity with unilateral and/or bilateral exophthalmia. The most prominent internal appearance was swelling of the internal organs with sanguineous ascetic fluid. There were 225 bacterial isolates found. Six species were identified through phenotypic and biochemical analysis; they were Aeromonas, Vibrio, Streptococcus, Pseudomonas, Enterococcus, and Edwardsiella spp., in descending percentage, respectively. Aeromonas spp., Vibrio spp., and Streptococcus spp. were the three most frequent isolated bacterial pathogens. The identification of Aeromonas hydrophila, Vibrio spp., and Streptococcus iniae, the three most common bacterial isolates, was confirmed by molecular analysis by polymerase chain reaction. Most of the tested strains were found to be responsive to Ciprofloxacin (CIP), Gentamicin (CN), and Chloramphenicol (C) but resistant to Amoxicillin (AMX), according to an antibiotic sensitivity test. The three most dangerous common bacterial infections discovered during mass-farmed tilapia summer mortality are A. hydrophil a, Vibrio sp., and S. iniae. This makes it clear that high water temperatures may raise the possibility of bacterial infections, which could cause widespread tilapia mortality and substantial financial losses. Therefore, it is crucial to maintain a beneficial fish culture, environment, and husbandry practices to enhance the tilapia-rearing environment and lessen the virulence of the disease. Isolated bacterial strains showed low levels of resistance to AMX but were vulnerable to CIP, CN, and C.

A new amino acid substitution in the MvALS1 gene of metsulfuron-methyl resistant biotypes Monochoria vaginalis (Burm. f.) C. Presl from West Java, Indonesia.

The most bothersome weed in rice fields in the Indonesian province of West Java is Monochoria vaginalis (Burm. F.) C. Presl, an aquatic herbaceous plant. Metsulfuron-methyl has long been used in wetland rice in West Java with a high enough intensity. However, the case of Monochoria vaginalis resistance to metsulfuron-methyl herbicides in Indonesia has not been widely reported and investigated. The study aims to (1) classify the resistance level of M. vaginalis toward metsulfuron-methyl, (2) identify Target Site Resistance (TSR) mechanism mutations in the MvALS1 gene of the resistant biotype of M. vaginalis. The Whole Plant Pot Test method was utilized to assess the resistance level of Monochoria vaginalis. Following that, all samples were subjected to DNA sequencing using the PCR method to identify mutations in the MvALS1 gene from the resistant biotype. After then, this study used DUET, a server with an integrated computational methodology, to anticipate the effect of mutations on protein stability. The result showed that Monochoria vaginalis from Rawamerta, Karawang showed a moderate level of resistance to metsulfuron-methyl with a resistance ratio of 6.00, Patokbeusi, Subang showed a low level of resistance to metsulfuron-methyl with a resistance ratio of 3.89, compared to susceptible Monochoria vaginalis. Nucleotide base alignment in the MvALS1 gene revealed that base substitutions occurred in the Monochoria vaginalis biotype from Rawamerta and Patokbeusi, resulting in 5 amino acid substitutions: Ser-64-Ala, Asp-66-Glu, Asn-240-Asp, Glu-426-Asn, and Ser-469-Asn and Sukra: Ser-64-Ala, Asp-66-Glu, and Asn-240-Asp. The analysis showed that S64A, D66E, and N240D stabilize the protein, whereas E426N and S469N destabilize it. This study confirms for the first time that Ser-64-Ala, Asn-240-Asp, and Glu-426-Asn amino acid mutations were found in cases of M. vaginalis resistance to metsulfuron-methyl (ALS inhibitor).

Dual bombard by Cytomegalovirus and Mycobacterium tuberculosis in a renal transplantee

Abstract In the first year following an organ transplant, more than 80% of patients encounter a minimum of one occurrence of infection. Here, we report a case of coinfection of the Cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB) in a kidney transplantee. Computed tomography chest (CT chest) showed bilateral ground-glass opacities. By Cytomegalovirus DNA polymerase chain reaction, 9360 copies were detected in plasma. Cartridge-based nucleic acid amplification test from bronchial washings tested positive for MTB with very low-level resistance to rifampicin. He was started on category-I antitubercular therapy without rifampicin and intravenous valganciclovir. The clinical status of the patient improved after 1 month of treatment.