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BMC Plant Biology Oct 2023Peanut is an important oil crop worldwide. Peanut web blotch is a fungal disease that often occurs at the same time as other leaf spot diseases, resulting in substantial...
BACKGROUND
Peanut is an important oil crop worldwide. Peanut web blotch is a fungal disease that often occurs at the same time as other leaf spot diseases, resulting in substantial leaf drop, which seriously affects the peanut yield and quality. However, the molecular mechanism underlying peanut resistance to web blotch is unknown.
RESULTS
The cytological examination revealed no differences in the conidium germination rate between the web blotch-resistant variety ZH and the web blotch-susceptible variety PI at 12-48 hpi. The appressorium formation rate was significantly higher for PI than for ZH at 24 hpi. The papilla formation rate at 36 hpi and the hypersensitive response rate at 60 and 84 hpi were significantly higher for ZH than for PI. We also compared the transcriptional profiles of web blotch-infected ZH and PI plants at 0, 12, 24, 36, 48, 60, and 84 hpi using an RNA-seq technique. There were more differentially expressed genes (DEGs) in ZH and PI at 12, 36, 60, and 84 hpi than at 24 and 48 hpi. Moreover, there were more DEGs in PI than in ZH at each time-point. The analysis of metabolic pathways indicated that pantothenate and CoA biosynthesis; monobactam biosynthesis; cutin, suberine and wax biosynthesis; and ether lipid metabolism are specific to the active defense of ZH against YY187, whereas porphyrin metabolism as well as taurine and hypotaurine metabolism are pathways specifically involved in the passive defense of ZH against YY187. In the protein-protein interaction (PPI) network, most of the interacting proteins were serine acetyltransferases and cysteine synthases, which are involved in the cysteine synthesis pathway. The qRT-PCR data confirmed the reliability of the transcriptome analysis.
CONCLUSION
On the basis of the PPI network for the significantly enriched genes in the pathways which were specifically enriched at different time points in ZH, we hypothesize that serine acetyltransferases and cysteine synthases are crucial for the cysteine-related resistance of peanut to web blotch. The study results provide reference material for future research on the mechanism mediating peanut web blotch resistance.
Topics: Arachis; Transcriptome; Cysteine; Reproducibility of Results; Gene Expression Profiling; Acetyltransferases; Serine
PubMed: 37884908
DOI: 10.1186/s12870-023-04545-9 -
Antimicrobial Agents and Chemotherapy Nov 2023- complex (ABC) causes severe infections that are difficult to treat due to pre-existing antibiotic resistance. Sulbactam-durlobactam (SUL-DUR) is a targeted...
- complex (ABC) causes severe infections that are difficult to treat due to pre-existing antibiotic resistance. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by , including multidrug- and carbapenem-resistant strains. In a recent global surveillance study of 5,032 ABC clinical isolates collected from 2016 to 2021, less than 2% of ABC isolates had SUL-DUR MIC values >4 µg/mL. Molecular characterization of these isolates confirmed the primary drivers of resistance are metallo-β-lactamases or penicillin-binding protein 3 (PBP3) mutations, as previously described. In addition, this study shows that certain common PBP3 variants, such as A515V, are insufficient to confer sulbactam resistance and that the efflux of durlobactam by AdeIJK is likely to play a role in a subset of strains.
Topics: Sulbactam; Acinetobacter baumannii; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Monobactams; Microbial Sensitivity Tests
PubMed: 37843305
DOI: 10.1128/aac.00665-23 -
Poultry Science Dec 2023β-Lactam antibiotics are one of the most clinical importance in human and veterinary medicine because they are used for both preventive and therapeutic purposes against...
Current status of β-lactam antibiotic use and characterization of β-lactam-resistant Escherichia coli from commercial farms by integrated broiler chicken operations in Korea.
β-Lactam antibiotics are one of the most clinical importance in human and veterinary medicine because they are used for both preventive and therapeutic purposes against several gram-positive, gram-negative, and anaerobic organisms. In this study, it was confirmed that β-lactams (81.1%) were found to be significantly prescribed the most among 74 farms in 5 integrated broiler operations, and single prescription (84.6%), 2-day (41.5%) or 3-day (40.0%) administration, and 15 to 22 d of age (67.7%) administration was significantly higher in the farms (P < 0.05). Among the E. coli isolated from 74 farms in 5 integrated broiler operations, β-lactam-resistant E. coli isolates were detected more frequently in fecal sample (94.6%) than in dust sample (60.8%) (P < 0.05). The prevalence of MDR in β-lactam-resistant isolates, ranging from 88.1 to 96.5%, was significantly higher than that in non-β-lactam-resistant isolates (P < 0.05), without significant differences among operations. Of 466 β-lactam-resistant isolates, 432 (92.7%) isolates harbored β-lactamase genes. The non-extended-spectrum β-lactamase (ESBL) gene bla (81.8%) showed the highest prevalence among isolates, followed by the non-ESBL gene bla (6.4%) (P < 0.05). Five ESBL genes, SHV-12, OXA-1, CTX-M-27, CTX-M-55, and CTX-M-65, were found in 0.9 to 6.0% of the isolates. The pAmpC gene bla was detected in 17 isolates (3.6%). These results suggest that feces and dust are important reservoirs of antimicrobial-resistant bacteria, highlighting the need to strengthen farm management regulations, such as cleaning, disinfection, and litter disposal and to reduce the use of antibiotics in broiler operations.
Topics: Animals; Humans; Escherichia coli; Farms; Chickens; beta-Lactams; Escherichia coli Infections; Anti-Bacterial Agents; beta-Lactamases; Monobactams; beta Lactam Antibiotics; Dust; Republic of Korea
PubMed: 37839166
DOI: 10.1016/j.psj.2023.103091 -
MSystems Dec 2023Multidrug-resistant is a major threat to the health care system and is associated with poor outcomes in infected patients. The combined use of antibiotics has become an...
Multidrug-resistant is a major threat to the health care system and is associated with poor outcomes in infected patients. The combined use of antibiotics has become an important treatment method for multidrug-resistant bacteria. However, the mechanism for their synergism has yet to be explored.
Topics: Humans; Aztreonam; Escherichia coli; Clavulanic Acid; Amoxicillin-Potassium Clavulanate Combination; beta-Lactamases
PubMed: 37830827
DOI: 10.1128/msystems.00758-23 -
Journal of Global Antimicrobial... Dec 2023To characterize two Escherichia coli strains isolated from a patient pre- and post-treatment, using β-lactams and β-lactam/β-lactamase inhibitor combinations (BLBLIs).
OBJECTIVES
To characterize two Escherichia coli strains isolated from a patient pre- and post-treatment, using β-lactams and β-lactam/β-lactamase inhibitor combinations (BLBLIs).
METHODS
A combination of antibiotic susceptibility testing (AST) with whole genome sequencing using Illumina and Oxford Nanopore platforms. Long-read sequencing and reverse transcription-quantitative PCR were performed to determine the copy numbers and expression levels of antibiotic resistance genes (ARGs), respectively. Effect on fitness costs were assessed by growth rate determination.
RESULTS
The strain obtained from the patient after the antibiotic treatment (XH989) exhibited higher resistance to cefepime, BLBLIs and quinolones compared with the pre-treatment strain (XH987). Sequencing revealed IS26-mediated duplications of a IS26-fosA3-bla plasmid-embedded element in strain XH989. Long-read sequencing (7.4 G data volume) indicated a variation in copy numbers of bla within one single culture of strain XH989. Increased copy numbers of the IS26-fosA3-bla element were correlated with higher CTX-M-65 expression level and did not impose fitness costs, while facilitating faster growth under high antibiotic concentrations.
CONCLUSION
Our study is an example from the clinic how BLBLIs and β-lactams exposure in vivo possibly promoted the amplification of an IS26-multiple drug resistance (MDR) region. The observation of a copy number variation seen with the bla gene in the plasmid of the post-treatment strain expands our knowledge of insertion sequence dynamics and evolution during treatment.
Topics: Humans; Escherichia coli; Cephalosporins; DNA Copy Number Variations; beta-Lactamases; Anti-Bacterial Agents; Monobactams; beta-Lactamase Inhibitors; Drug Resistance, Microbial
PubMed: 37802302
DOI: 10.1016/j.jgar.2023.09.018 -
Microbiology Spectrum Dec 2023The increased feasibility of whole-genome sequencing has generated significant interest in using such molecular diagnostic approaches to characterize difficult-to-treat,...
The increased feasibility of whole-genome sequencing has generated significant interest in using such molecular diagnostic approaches to characterize difficult-to-treat, antimicrobial-resistant (AMR) infections. Nevertheless, there are current limitations in the accurate prediction of AMR phenotypes based on existing AMR gene database approaches, which primarily correlate a phenotype with the presence/absence of a single AMR gene. Our study utilized a large cohort of cephalosporin-susceptible bacteremia samples to determine how increasing the dosage of narrow-spectrum β-lactamase-encoding genes in conjunction with other diverse β-lactam/β-lactamase inhibitor (BL/BLI) genetic determinants contributes to progressively more severe BL/BLI phenotypes. We were able to characterize the complexity of the genetic mechanisms underlying progressive BL/BLI resistance including the critical role of β-lactamase encoding gene amplification. For the diverse array of AMR phenotypes with complex mechanisms involving multiple genomic factors, our study provides an example of how composite risk scores may improve understanding of AMR genotype/phenotype correlations.
Topics: Humans; beta-Lactamase Inhibitors; Escherichia coli; Anti-Bacterial Agents; Lactams; Escherichia coli Infections; Phenotype; beta-Lactams; Monobactams; beta-Lactamases; Microbial Sensitivity Tests
PubMed: 37800937
DOI: 10.1128/spectrum.02221-23 -
The Journal of Antimicrobial... Nov 2023The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For...
BACKGROUND
The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.
OBJECTIVES
To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).
METHODS
Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.
RESULTS
Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.
CONCLUSIONS
These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.
Topics: Humans; Cefepime; Aztreonam; Anti-Bacterial Agents; Ceftazidime; Piperacillin; Microbial Sensitivity Tests; Monte Carlo Method
PubMed: 37796958
DOI: 10.1093/jac/dkad300 -
Journal of Clinical Microbiology Oct 2023Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination is a treatment option for infections due to carbapenem-resistant...
Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination is a treatment option for infections due to carbapenem-resistant Enterobacterales (CRE), including metallo-ß-lactamase producers, regardless of additional production of broad-spectrum serine-ß-lactamases. However, AZA-resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster and more accurate clinical decision-making. We therefore developed a rapid culture-based test for the identification of AZA resistance among multidrug-resistant Enterobacterales. The Rapid Aztreonam/Avibactam NP test is based on resazurin reduction when bacterial growth occurs in the presence of AZA at 8/4 µg/mL (protocol 1) or 12/4 µg/mL (protocol 2). Given the absence of guidelines on AZA susceptibility testing, two tentative breakpoints were indeed used to categorize AZA-susceptible isolates: ≤4 µg/mL in protocol 1 and ≤ 8 µg/mL in protocol 2. Bacterial growth was visually detectable by a blue-to-purple or blue-to-pink color change of the medium. A total of 78 enterobacterial isolates (among which 34 AZA-resistant and 13 AZA-resistant according to protocols 1 and 2, respectively) were used to evaluate the test performance using protocol 1 or protocol 2. The sensitivity and specificity of the test were found to be 100% and 97.7%, respectively, following protocol 1 and 100% and 100%, respectively, following protocol 2, in comparison with broth microdilution. All results were obtained within 4.5 hours corresponding to a time saving of ca. 14 hours compared with currently available methods for AZA susceptibility testing. The Rapid Aztreonam/Avibactam NP test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine.
Topics: Humans; Aztreonam; Anti-Bacterial Agents; beta-Lactamases; Azabicyclo Compounds; beta-Lactamase Inhibitors; Microbial Sensitivity Tests; Drug Combinations; Ceftazidime
PubMed: 37791761
DOI: 10.1128/jcm.00588-23 -
The New England Journal of Medicine Oct 2023Ceftobiprole is a cephalosporin that may be effective for treating complicated bacteremia, including methicillin-resistant . (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ceftobiprole is a cephalosporin that may be effective for treating complicated bacteremia, including methicillin-resistant .
METHODS
In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed.
RESULTS
Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole.
CONCLUSIONS
Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.).
Topics: Adult; Humans; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Daptomycin; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Double-Blind Method; Administration, Intravenous; Aztreonam
PubMed: 37754204
DOI: 10.1056/NEJMoa2300220 -
International Journal of Antimicrobial... Nov 2023Combination therapy can enhance the activity of available antibiotics against multidrug-resistant Gram-negative bacteria. This study assessed the effects of polymyxin B...
BACKGROUND
Combination therapy can enhance the activity of available antibiotics against multidrug-resistant Gram-negative bacteria. This study assessed the effects of polymyxin B combinations against carbapenemase-producing Klebsiella pneumoniae (K. pneumoniae).
METHODS
Twenty clinical K. pneumoniae strains producing NDM-1 (n = 8), OXA-48-like (n = 10), or both NDM-1 and OXA-48-like (n = 2) carbapenemases were used. Whole-genome sequencing was applied to detect resistance genes (e.g. encoding antibiotic-degrading enzymes) and sequence alterations influencing permeability or efflux. The activity of polymyxin B in combination with aztreonam, fosfomycin, meropenem, minocycline, or rifampicin was investigated in 24-hour time-lapse microscopy experiments. Endpoint samples were spotted on plates with and without polymyxin B at 4 x MIC to assess resistance development. Finally, associations between synergy and bacterial genetic traits were explored.
RESULTS
Synergistic and bactericidal effects were observed with polymyxin B in combination with all other antibiotics: aztreonam (11 of 20 strains), fosfomycin (16 of 20), meropenem (10 of 20), minocycline (18 of 20), and rifampicin (15 of 20). Synergy was found with polymyxin B in combination with fosfomycin, minocycline, or rifampicin against all nine polymyxin-resistant strains. Wildtype mgrB was associated with polymyxin B and aztreonam synergy (P = 0.0499). An absence of arr-2 and arr-3 was associated with synergy of polymyxin B and rifampicin (P = 0.0260). Emergence of populations with reduced polymyxin B susceptibility was most frequently observed with aztreonam and meropenem.
CONCLUSION
Combinations of polymyxin B and minocycline or rifampicin were most active against the tested NDM-1 and OXA-48-like-producing K. pneumoniae. Biologically plausible genotype-phenotype associations were found. Such information might accelerate the search for promising combinations and guide individualised treatment.
Topics: Polymyxin B; Aztreonam; Meropenem; Klebsiella pneumoniae; Minocycline; Fosfomycin; Rifampin; Drug Synergism; Anti-Bacterial Agents; beta-Lactamases; Microbial Sensitivity Tests
PubMed: 37716575
DOI: 10.1016/j.ijantimicag.2023.106967