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At least 19 recordsLinked to original sources
PubMed2026

Long-read sequencing reveals putatively mobilizable resistance genes and multi-drug resistance plasmids underestimated by short-read metagenomics.

While shotgun metagenomics is often used to profile antibiotic resistome in gut microbial communities, few studies have investigated if the choice of sequencing platform and assembly strategy affect what mobile genetic elements and antimicrobial resistance genes are recovered. In this study, we compared three platforms (Illumina, Oxford Nanopore, and PacBio HiFi) and seven assembly strategies on gut metagenomes from cattle, pig, and human as case studies. Long-read assemblies recovered 5- to 7-fold more plasmid sequence than Illumina in cattle and pig (mean 17.0 Mb vs. 3.1 Mb), while Illumina performed comparably in the less diverse human gut where high per-species coverage enabled effective short-read plasmid assembly. Long reads also detected more resistance genes on plasmid contigs. Hybrid assembly results depended on the algorithm: scaffolding-based OPERA-MS preserved long-read contiguity and recovered more plasmid-borne resistance genes, while the short-read-centric metaSPAdes hybrid mode produced fragmented assemblies. After collapsing haplotype redundancy, PacBio HiFi identified 2 and 49 unique multi-drug resistance plasmid lineages in cattle and pig, respectively. On the other hand, only 2 and 4 were identified from Illumina. Long reads also placed far more ARGs in a putative mobilization context (50-73%) compared to 14-21% for short reads. Platform and assembly strategy are thus key variables in mobilome and resistome characterization and should be accounted for in antimicrobial resistance surveillance.

Animals↗
PubMed2025

Effects of recombination on multi-drug resistance evolution in Plasmodium falciparum malaria.

When multiple beneficial alleles at multiple loci are present in a population but not linked together in any one individual, there is no general evolutionary result that determines whether recombination will speed up or slow down the emergence and evolution of genotypes carrying multiple beneficial alleles. Translated to infectious disease control, this evolutionary uncertainty means that when multiple types of drug resistance are present we do not know whether recombination will act more strongly to (1) bring together single-resistant genotypes into multi-drug resistant (MDR) genotypes, or (2) break apart MDR genotypes into single-resistant genotypes. In this paper, we introduce a new version of an established and validated individual-based malaria transmission model where we have added 25 drug-resistance related loci, individual mosquito bites, and mosquitoes feeding on multiple hosts in a single meal (interrupted feeds) allowing for recombination events of different Plasmodium falciparum genotypes from different hosts. Recombination among P. falciparum genotypes in this model occurs from two sources of variation, multi-clonal infections in single hosts and interrupted feeds on multiple hosts, and we show that 80% to 97% of MDR recombinant falciparum genotypes are projected to occur from single uninterrupted bites on hosts with multi-clonal infections (for malaria prevalence > 5%). Increases in the model's interrupted feeding rate slowly increase the number of recombination events occurring from interrupted feeds. A comparison of drug-resistance management strategies with this new model shows that, over a 15-year timeframe, triple artemisinin-combination therapies (ACT) strategies show the largest reductions in treatment failures and the longest delays until artemisinin resistance reaches a critical 1% threshold. Multiple first-line therapies (MFT) are second best under these criteria, and ACT cycling approaches are third best. When compared to cycling strategies, MFT strategies generate a greater diversity of recombinant genotypes but fewer recombination events generating MDR and slower emergence of these recombinant MDR genotypes.

Plasmodium falciparum↗
PubMed1977

[Transfer of multi-drug resistance in vivo by salmonellae and shigella in white mice].

The oral infection accomplished by 0.3 cm3 X 10(10) microbial bodies of Salmonella heidelberg and Shigella sonnei in albino mice the pathogens were found to localize in the intestines. The Salmonellae were detected up to the 10th day, and the Shigellae--up to the 14th day. Both Shigella and Salmonella transferred multi-drug resistance to some enterobacteria--E. coli and Proteus as well as to Salmonella typhimurium when the latter was also present in the intestinal tract; of these some 10--40 per cent acquire the multi-drug resistance of Salmonella heidelberg and Shigella sonnei. This type of resistance was most often transferred en bloc for the six, resp., eight markers. On some occasions segregation was observed with the transference of particular markers only.

Animals↗
PubMed2026

[Genomic characteristics of multi-drug resistant of non-O1/non-O139 Vibrio cholerae ST1565 from sepsis cases].

To analyze the genomic characteristics of multi-drug resistant of non-O1/non-O139 Vibrio cholerae ST1565 from sepsis cases. An 88 years old male patient admitted to Huashan Hospital in Shanghai on July 2, 2025, who was retrospectively analyzed. The clinical diagnosis was severe bacterial enteritis and secondary NOVC sepsis. Blood culture confirmed the presence of non-O1/non-O139 group Vibrio cholerae. The strain was a multidrug-resistant isolated of ST1565 as determined by whole-genome sequencing. The ResFinder database predicted 11 resistance genes for 6 classes of antibiotics: qnrVC5, sul2, floR, tet(59), aph(6)-Id, aph(3'')-Ib, dfrA15, dfrA31, almE, almF, and almG. Except for the quinolone qnrVC5, which was not expressed, the other resistance genes were consistent matched the phenotypic results. Additionally, 8 insertion sequences were identified: ISVch1, ISVvu4, ISVch6, ISVvu8, ISVpa3, ISVpa4, ISVsa3, and ISShfr9. Important virulence factors included 3 secreted protein toxin genes: Vibrio cholerae hemolysin, repeat toxin, and Vibrio parahaemolyticus thermostable direct hemolysin. The patient was cured after sequential treatment with meropenem, levofloxacin, and doxycycline. NOVC/ST1565 is a newly identified sequence type in China, which exhibits multidrug-resistant and hypervirulent phenotypes.

Drug Resistance, Multiple, Bacterial↗
PubMed2026

Dual-species interactions with intestinal bacteria drive multi-drug resistance in Campylobacter.

OBJECTIVES: Multidrug-resistant (MDR) Campylobacter infections are an increasing clinical concern, as rising fluoroquinolone (FQ) resistance leaves macrolides as the primary treatment option. We investigated multidrug resistance in clinical Campylobacter samples from Germany. METHODS: We analyzed 6980 clinical isolates (2010-2022), performing phenotypic susceptibility testing and sequencing on 2912 genomes. Cultures showing multidrug resistance were studied using scanning electron microscopy (SEM). RESULTS: We found that 453 (6%) Campylobacter samples were resistant to both FQ and macrolides. Two of the C. jejuni samples were resistant to antibiotics from ten different classes. Genome analysis revealed that these samples, despite being derived from single colonies, contained >10% Enterococcus DNA reads. SEM confirmed the presence of coccoid bacteria interspersed with spiral-shaped Campylobacter. Additional culture-based purification resulted in pure C. jejuni isolates that retained FQR but lost macrolide resistance. The presence of MDR Enterococcus spp. in the mixed samples protected C. jejuni from above-MIC (minimum inhibitory concentration) concentrations of several ribosome-targeting antimicrobials whereas pure Campylobacter were susceptible. CONCLUSIONS: The impact of microbial interactions on resistance phenotypes is poorly understood. We show that close interactions with highly resistant intestinal bacteria can induce multidrug resistance phenotypes in Campylobacter. These findings highlight that microbial context shapes antibiotic resistance and may influence treatment outcomes.

Campylobacter jejuni↗
PubMed2025

Ergosterol-depleted clinical isolates of Nakaseomyces glabratus can develop multi-drug resistance without apparent fitness and virulence defects.

OBJECTIVES: Nakaseomyces glabratus (formerly Candida glabrata) is a leading cause of invasive candidiasis and rapidly develops antifungal drug resistance during treatment. An increasing number of clinical isolates shows reduced susceptibility to echinocandins and azoles, leaving amphotericin B (AMB) as a last therapeutic option. Resistance of N. glabratus to this drug is rare and its underlying mechanisms are still not fully understood. Here, we describe two independent multidrug resistant (MDR) bloodstream isolates displaying resistance to AMB and anidulafungin (ANF) as well as a reduced susceptibility to azoles. METHODS: Whole-genome sequencing and sterol profiling were performed on nine clinical N. glabratus isolates which were resistant to ANF and displayed resistance or low susceptibility to fluconazole (FLU) and AMB. The transcriptional response of reference strain CBS138 and an AMBR+ANFR isolate was analyzed by RNA-seq. Furthermore, PDR1 was deleted in the latter isolate to examine its influence on efflux pump gene expression. Additionally, fitness and virulence of the AMBR+ANFR isolate were examined in growth assays and a Galleria mellonella infection model. RESULTS: Loss of function mutations in the genes ERG3 and ERG4 is linked to ergosterol depletion and AMB resistance. Ergosterol depletion also contributed to a Pdr1-mediated up-regulation of ERG and ABC transporter genes which was associated with low FLU susceptibility. The AMBR isolates displayed no fitness defects and one of them was fully virulent in a G. mellonella infection model. CONCLUSIONS: These findings demonstrate that ergosterol depletion in N. glabratus leads to AMB resistance without affecting fitness or virulence.

Journal Article↗
PubMed1977

[Experimental transmission of antibiotic resistance in chicks].

Multi-drug resistance of Salmonella heidelberg was transmitted to normal intestinal flora (E. coli organisms were resistant to ampicillin, streptomycin, tetracycline, erythromycin, and oleandomycin. The donor strains of Salmonella heidelberg used in the experiment was a carrier of the following nine markers of resistance: ampicillin, streptomycin, chloramphenicol, kanamycin, neomycin, novobiocin, tetracycline, erythromycin, and oleandomycin. The donor strains of Salmonella heidelberg used in the experiment was a carrier of the following nine markers of resistance: ampicillin, streptomycin, chloramphenicol, kanamycin, neomycin, novobiocin, tetracycline, erythromycin, and oeandomycin, novobiocin, tetracycline, erythromycin, and oleandomycin. The resistance to drugs was transmitted with the oral administration of the donor strain at the preliminary neutralization of the action of hydrochloric acid in the stomah secretion through sodium bicarbonate (1 cm3 of a 10 per cent sol.) an hour prior to feeding the birds with Salmonella heidelberg (1 cm3 of 10(10). In other experiments carboneum tetrachloratum was injected at rates of 0.08 to 0.15 cm3 (acocrting with the body weight of birds) one day prior to infection, followed by the administration of 0.20 to 0.40 cm3 of a 2 per cent solution of omnopon. Escherichia coli organisms acquired new markers of resistance--to chloramphenicol, kanamycin, neomycin and novobiocin. The level of resistance proved equal with that to the donor strain. A total of 1.8 to 5.4 per cent of the intestinal E. coli investigated proved to be carriers of the indicated markers of resitance. Highest level in acquiring markers of multi-drug resistance (13 per cent) showed E. coli organisms isolated from the liver of birds injected additionally with C. tetrachloratum omnopon.

Animals↗
PubMed2021

Whole-genome sequencing-based phylogeny, antibiotic resistance, and invasive phenotype of Escherichia coli strains colonizing the cervix of women in preterm labor.

BACKGROUND: Escherichia coli is a major neonatal pathogen and the leading cause of early-onset sepsis in preterm newborns. Maternal E. coli strains are transmitted to the newborn causing invasive neonatal disease. However, there is a lack of data regarding the phenotypic and genotypic characterization of E. coli strains colonizing pregnant women during labor. METHODS: This prospective study performed at the University of Oklahoma Medical Center (OUHSC) from March 2014 to December 2015, aimed to investigate the colonization rate, and the phylogeny, antibiotic resistance traits, and invasive properties of E. coli strains colonizing the cervix of fifty pregnant women diagnosed with preterm labor (PTL). Molecular analyses including bacterial whole-genome sequencing (WGS), were performed to examine phylogenetic relationships among the colonizing strains and compare them with WGS data of representative invasive neonatal E. coli isolates. Phenotypic and genotypic antibiotic resistance traits were investigated. The bacteria's ability to invade epithelial cells in vitro was determined. RESULTS: We recruited fifty women in PTL. Cervical samples yielded E. coli in 12 % (n=6). The mean gestational age was 32.5 (SD±3.19) weeks. None delivered an infant with E. coli disease. Phenotypic and genotypic antibiotic resistance testing did not overall demonstrate extensive drug resistance traits among the cervical E. coli isolates, however, one isolate was multi-drug resistant. The isolates belonged to five different phylogroups, and WGS analyses assigned each to individual multi-locus sequence types. Single nucleotide polymorphism-based comparisons of cervical E. coli strains with six representative neonatal E. coli bacteremia isolates demonstrated that only half of the cervical E. coli isolates were phylogenetically related to these neonatal invasive strains. Moreover, WGS comparisons showed that each cervical E. coli isolate had distinct genomic regions that were not shared with neonatal E. coli isolates. Cervical and neonatal E. coli isolates that were most closely related at the phylogenetic level had similar invasion capacity into intestinal epithelial cells. In contrast, phylogenetically dissimilar cervical E. coli strains were the least invasive among all isolates. CONCLUSIONS: This pilot study showed that a minority of women in PTL were colonized in the cervix with E. coli, and colonizing strains were not phylogenetically uniformly representative of E. coli strains that commonly cause invasive disease in newborns. Larger studies are needed to determine the molecular characteristics of E. coli strains colonizing pregnant women associated with an increased risk of neonatal septicemia.

Adult↗
PubMed1979

[Transmissible drug resistance in strains of E. coli isolated from birds].

A total of 97 strains of Escherichia coli, resistant either to one or to several theraupeutic agents and isolated from young and adult birds, were studied for the presence of transmissible R plasmids. Transmissible drug resistance was demonstrated with 37 per cent of the strains. The transmission of such resistance was manifested in highest percent in the case of ampicillin and chloramphenicol, followed by sulphathiazole and tetracycline. The R plasmids established in multi-drug resistant strains with three markers and more, were found to bear high percent determinants of resistance to chloramphenicol and in lower percent such to sulphathiazole and tetracycline. The same strains presented R plasmids that bore determinants of resistance to five therapeutic agents (Tc, Su, Cm, Mm, Nm) and to three therapeutic agents (Cm, Ap, Tc) and (Cm, Su, Km).

Animals↗
PubMed1979

Nosocomial klebsiellas. I. Colonization of hospitalized patients.

The colonization of patients by Klebsiella and several other gram-negative bacteria was studied in a hospital urological ward over a period of six months. Before and during the survey there was no evidence of an outbreak of nosocomial infection and multi-drug resistant strains of Klebsiella were not isolated. Klebsiella were biotyped by nine biochemical tests, which led to the detection of 66 biotypes spread uniformly throughout the survey period. This method of biotyping proved a useful epidemiological tool. The colonization rate of throats, hands, and faeces of patients increased after admission to the ward, especially when antibiotics were used. The effect of systemic antibiotics was greater than that of urinary antibiotics especially on throat and faeces carrier rates. Carrier rates for Klebsiella increased also after catheterization and operation--relationships which could well be multifactorial. During the first two weeks after admission the proportion of antibiotic resistant strains of Klebsiella in carriers increased. The proportion of resistant strains amongst isolations from clinical infections was always greater than among strains isolated routinely from sites of carriage.

Anti-Bacterial Agents↗
PubMed2025

Demixer: a probabilistic generative model to delineate different strains of a microbial species in a mixed infection sample.

MOTIVATION: Multi-drug resistant or hetero-resistant tuberculosis (TB) hinders the successful treatment of TB. Hetero-resistant TB occurs when multiple strains of the TB-causing bacterium with varying degrees of drug susceptibility are present in an individual. Existing studies predicting the proportion and identity of strains in a mixed infection sample rely on a reference database of known strains. A main challenge then is to identify de novo strains not present in the reference database, while quantifying the proportion of known strains. RESULTS: We present Demixer, a probabilistic generative model that uses a combination of reference-based and reference-free techniques to delineate mixed infection strains in whole genome sequencing (WGS) data. Demixer extends a topic model widely used in text mining to represent known mutations and discover novel ones. Parallelization and other heuristics enabled Demixer to process large datasets like CRyPTIC (Comprehensive Resistance Prediction for Tuberculosis: an International Consortium). In both synthetic and experimental benchmark datasets, our proposed method precisely detected the identity (e.g. 91.67% accuracy on the experimental in vitro dataset) as well as the proportions of the mixed strains. In real-world applications, Demixer revealed novel high confidence mixed infections (101 out of 1963 Malawi samples analysed), and new insights into the global frequency of mixed infection (2% at the most stringent threshold in the CRyPTIC dataset) and its significant association to drug resistance. Our approach is generalizable and hence applicable to any bacterial and viral WGS data. AVAILABILITY AND IMPLEMENTATION: All code relevant to Demixer is available at https://github.com/BIRDSgroup/Demixer.

Mycobacterium tuberculosis↗
PubMed2025

Comparison of phylogenetic metrics of transmission in symptomatic and asymptomatic tuberculosis.

BACKGROUND: Understanding drivers of Mycobacterium tuberculosis (Mtb) transmission remains a critical challenge in high-burden settings. Tuberculosis control efforts traditionally target symptomatic individuals, yet the role of asymptomatic cases in sustaining transmission is increasing recognized. METHODS: We conducted a genomic and epidemiological analysis of Mtb isolates collected in Mato Grosso do Sul, Brazil, between 2008 and 2024. From 2017 to 2022, active case finding was performed in three of the state's largest prisons, whereby sputum was collected from individuals irrespective of symptoms and tested by GeneXpert and culture. We evaluated several metrics of recent transmission from symptomatic and asymptomatic individuals, including phylogenetic clustering, Time-scaled Haplotype Density (THD), Local Branching Index (LBI), and transmission probabilities inferred using the Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories (BREATH). FINDINGS: We sequenced 2,362 Mtb strains, of which 3.5% (115/2,362) were resistant to at least one drug, and 0.6% (16/2,362) were multi-drug resistant. Most strains were lineage 4, and 78.2% of all isolates were part of a genomic cluster. Among 2,362 individuals with tuberculosis, 1,137 were incarcerated at the time of diagnosis. Among these, 505 were identified through active case finding: 277 had symptomatic disease and 228 had asymptomatic tuberculosis. There was no significant difference in phylogenetic clustering proportion (77% vs. 85%; p= 0.816), THD (median 0.50 vs. 0.39; p = 0.120), or LBI (median 0.00863 vs. 0.00871; p = 0.086) between symptomatic and asymptomatic individuals. Bayesian transmission trees revealed no significant difference in the number of secondary infections inferred from symptomatic compared with asymptomatic individuals (p = 0.56). These findings were consistent across genomic clusters and robust to model assumptions. INTERPRETATION: We identified no differences in transmission from symptomatic compared with asymptomatic individuals, using several genomic measures of transmission, underscoring the substantial contribution that asymptomatic tuberculosis makes to transmission at the population level.

Asymptomatic↗
PubMed1979

Antagonistic effects of Bacillus natto and Streptococcus faecalis on growth of Candida albicans.

The growth-inhibitory effects of Bacillus natto and Streptococcus faecalis on Canida albicans were investigated. When inoculated into the filtrate of a long-term culture of B. natto strain BN (BN), a stock culture of C. albicans RIMD 0301020 lost its viability completely, whereas C. albicans RIMD 0301011, a fresh isolate from a clinical source, did not. In continuous flow (CF) culture the growth of both strains of C. albicans was suppressed by mixed cultivation with BN. On the other hand, in classical batch culture BN did not suppress the growth of C. albicans. S. faecalis BIO-4R, a multi-drug resistant strain, was also antagonistic to C. albicans RIMD 0301011 but symbiotic with BN in CF culture. These findings suggest that BN in concert with S. faecalis BIO-4R may inhibit the growth of C. albicans in the intestinal tract.

Bacillus↗
PubMed1978

Evaluation of an office method of detecting bacteriuria.

Although catheter-associated UTI continues to be the leading cause of nosocomial infection, epidemiological investigation of catheter use in many hospitals may be precluded by the reluctance of the laboratory to process the large number of urine cultures. We have evaluated the use by Nurse Epidemiologists of Bacturcult tubes for such purposes. The urine of 111 catheterized patients was cultured daily using both the Bacturcult and streak plate method until significant bacteriuria developed (greater than 10(5) colonies/ml). Bacturcult proved as accurate as the conventional technique in detecting bacteriuria. In contrast to previous studies, the daily incidence of infection rose with increasing duration of catheterization. Concomitant antibiotic usage reduced the risk of infection but selected out multi-drug resistant organisms. Older age and procedural errors also increased the risk of infection. The study took 150 hours to complete and cost about $250. It is concluded that Bacturcult is an accurate, simple and relatively inexpensive method of detecting bacteriuria and could be useful for investigating the epidemiology of catheter-associated infections in community hospitals.

Adult↗
PubMed2025

Molecular characterization of drug-resistance genes and dynamics of multidrug-resistant Salmonella spp. in waterfowl: a pre- and post-antibiotic ban surveillance in Guangdong, China from 2013 to 2023.

BACKGROUND: Multidrug-Resistant Organism (MDRO) refers to bacteria that are Resistant to three or more types of antibiotics in clinical use. The global health threat posed by multidrug-resistant (MDR) bacterial pathogens and their cross-species transmission necessitates rigorous Surveillance. This urgency is amplified in China where antibiotic growth promoters were widely used in animal husbandry until the 2020 implementation of Announcement No. 194 launched by Ministry of Agriculture and Rural Affairs (Announcement 194), banning non-therapeutic antibiotics in feed. This study conducted a decade long investigation on the correlation between antimicrobial resistance (AMR) phenotypes and genetic determinants in 314 Salmonella isolates collected from waterfowl across Guangdong Province, China, utilizing disk diffusion (Kirby-Bauer method) and PCR-based detection of antibiotic resistance genes (ARGs). The study period covered the antibiotic policy transition in China, specifically encompassing the pre-ban (2013-2019) and post-ban (2020-2023) phases of the nationwide prohibition on growth-promoting antimicrobials in animal feed. METHODS: Antimicrobial Susceptibility profiles against 16 agents were determined via Kirby-Bauer testing, while PCR amplification targeted 20 ARGs. Statistical analyses evaluated phenotype-genotype correlations using Pearson`s chi-square test. RESULTS: Surveillance revealed escalating resistance rates annually. Highest resistance prevalence was observed against &#x3b2;-lactams and amphenicols (92.25%), whereas amikacin exhibited the lowest resistance rate (9.55%). MDR prevalence reached 87.23%, with the AMP-CAZ-GEN-FFC-TET resistance profile predominating (51.6% of isolates). Genetic analysis identified 3 to 16 ARGs per isolate was harboring, with blaTEM demonstrating the highest detection frequency (90.76%). Significant phenotype-genotype correlations (p&#x2009;<&#x2009;0.05) were observed for 13 genes: blaCTX-M, blaTEM, blaOXA, aacC2, aph(3')-I, aac(3)-IV, aadA1, qnrS, qnrA, clmA, floR, sulII, tetA. Notably, significant declines in resistance to aminoglycosides (e.g., gentamicin from 71.7 to 3.5%) and florfenicol (from 81.1 to 9.6%) were observed after China's 2019 antibiotic ban policy (p&#x2009;<&#x2009;0.001), underscoring the impact of targeted antimicrobial stewardship in avian husbandry. CONCLUSIONS: Analysis of 314 waterfowl Salmonella strains revealed severe multidrug resistance (MDR) and diverse resistance genes (DRGs), with 13 DRGs linked to resistance. China's antibiotic ban reduced targeted resistance, but MDR persists alarmingly via acquired DRGs and adaptation. Continued enforcement may lower aminoglycoside/phenicol resistance, but &#x3b2;-lactam resistance will likely endure, worsened by transcontinental blaCTX-M spread. Critically, plasmid co-selection threatens to amplify MDR, demanding genomic surveillance. Mitigation requires boosting policy compliance, developing non-antibiotic therapies, mapping mutations, establishing cross-species barriers, and prioritizing One Health interventions to block resistance spread.

China↗
PubMed2026

Comparative genomics reveals genotype-phenotype concordance and cryptic resistomes in clinical Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen because of its adaptability. It shows rapid evolution of multidrug resistance (MDR). Phenotype-based diagnostics often fail to detect silent resistance determinants and early adaptive changes. This study integrates phenotypic profiling with whole-genome sequencing (WGS) to examine resistance architecture in clinical isolates from eastern India. METHODS: From 1295 culture-positive P. aeruginosa specimens collected at a tertiary care hospital in eastern India. Using predefined criteria, representative MDR and non-MDR isolates were selected, including distinct resistance phenotypes, specimen-source diversity, and hospital and community-acquired settings; multivariate analysis of resistance profiles illustrated phenotypic diversity. Antimicrobial susceptibility assessed using VITEK-2 and Kirby-Bauer disk diffusion, species identity confirmed by 16&#xa0;S rRNA sequencing, and genomic analysis processed through a reference-guided workflow. Antimicrobial Resistance (AMR) determinants were identified through CARD, and phylogenetic tree constructed from 454 publicly available P. aeruginosa genomes. RESULTS: MDR exhibited greater sequence divergence relative to PA14 (~&#x2009;69,000 variants) than the non-MDR isolate (~&#x2009;58,700 variants), with >&#x2009;92% coverage at &#x2265;&#x2009;30X depth. Strong genotype-phenotype concordance observed in MDR isolates across five antibiotic classes, associated with &#x3b2;-lactamase variants (PDC-67, OXA-396) and regulatory adaptations (ArmR, cprS). The non-MDR isolate harboured gyrA (T83I) resistance-associated mutations, PDC-1, and OXA-847 without phenotypic expression, indicating silent resistome. Phylogenetically, MDR isolates clustered tightly within the phylogeny, while the non-MDR isolate formed a distinct lineage. CONCLUSION: Observed genomic differences align with adaptation under antimicrobial selection, though confirmation requires larger collections. The non-MDR isolate retained a silent resistome. Findings highlight limitations of phenotype-only diagnostics, support genomic data integration, and emphasize transcriptomics for hidden resistance expression and regulatory dynamics.

Pseudomonas aeruginosa↗
PubMed1978

Repeated use of L-asparaginase in multi-drug therapy of childhood leukemia.

The capacity of 1-asparaginase in two separate schedules (consecutive and intermittent), along with vincristine and prednisone to produce multiple responses, was evaluated in previously treated children with acute leukemia in relapse. The response rates varied inversely with previous 1-asparaginase exposure. A history of prior resistance to prednisone and vincristine appeared to reduce the response rate. Hypersensitivity reactions occurred in 14%.

Acute Disease↗