A Foundation Model Identifies Broad-Spectrum Antimicrobial Peptides against Drug-Resistant Bacterial Infection DOI Creative Commons
Tingting Li,

Xuanbai Ren,

Xiaoli Luo

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 30, 2024

Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, AMPs. Using deepAMP to reduce enhance membrane-disrupting abilities AMPs, we identify, synthesize, experimentally test 18 T1-AMP (Tier 1) 11 T2-AMP 2) candidates in two-round design by employing cross-optimization-validation. More than 90% designed AMPs show better inhibition penetratin both Gram-positive (i.e., S. aureus) Gram-negative bacteria K. pneumoniae P. aeruginosa). T2-9 shows strongest antibacterial activity, comparable FDA-approved antibiotics. that three (T1-2, T1-5 T2-10) significantly aureus compared ciprofloxacin are effective against skin wound infection female mouse model infected with aeruginosa. In summary, expedites discovery effective, drug-resistant bacteria.

Language: Английский

Klebsiella oxytoca Complex: Update on Taxonomy, Antimicrobial Resistance, and Virulence DOI
Jing Yang, Haiyan Long, Ya Hu

et al.

Clinical Microbiology Reviews, Journal Year: 2021, Volume and Issue: 35(1)

Published: Dec. 1, 2021

Klebsiella oxytoca is actually a complex of nine species-Klebsiella grimontii, huaxiensis, michiganensis, K. oxytoca, pasteurii, spallanzanii, and three unnamed novel species. Phenotypic tests can assign isolates to the complex, but precise species identification requires genome-based analysis. The human commensal also an opportunistic pathogen causing various infections, such as antibiotic-associated hemorrhagic colitis (AAHC), urinary tract infection, bacteremia, has caused outbreaks. Production cytotoxins tilivalline tilimycin lead AAHC, while many virulence factors seen in pneumoniae, capsular polysaccharides fimbriae, have been found complex; however, their association with pathogenicity remains unclear. Among 5,724 clinical SENTRY surveillance system, rates nonsusceptibility carbapenems, ceftriaxone, ciprofloxacin, colistin, tigecycline were 1.8%, 12.5%, 7.1%, 0.8%, 0.1%, respectively. Resistance carbapenems increasing alarmingly. In addition intrinsic blaOXY, genes encoding β-lactamases varying spectra hydrolysis, including extended-spectrum β-lactamases, few CTX-M variants several TEM SHV variants, found. blaKPC-2 most common carbapenemase gene mainly on IncN or IncF plasmids. Due ability acquire antimicrobial resistance carriage multiple genes, potential become major threat health.

Language: Английский

Citations

116

Finding Order in the Chaos: Outstanding Questions in Klebsiella pneumoniae Pathogenesis DOI Creative Commons
Shekina Gonzalez-Ferrer, Hernán F. Peñaloza, James A. Budnick

et al.

Infection and Immunity, Journal Year: 2021, Volume and Issue: 89(4)

Published: Feb. 4, 2021

Klebsiella pneumoniae are Gram-negative facultative anaerobes that found within host-associated commensal microbiomes, but they can also cause a wide range of infections often difficult to treat. These caused by different pathotypes K. pneumoniae, called either classical or hypervirulent strains. two groups genetically distinct, inhabit nonoverlapping geographies, and types harmful in humans. distinct bacterial have been interact differently with the host immune system. Initial innate defenses against infection include complement, macrophages, neutrophils, monocytes; these primary strategies employed clear infections. pathogenesis depends upon interactions between microbe each defenses, it is becoming increasingly apparent genetic diversity impacts outcomes interactions. Here, we highlight recent advances our understanding pathogenesis, focus on how evolution impact mammalian defenses. We discuss outstanding questions regarding frustrate normal responses, capitalize states immunocompromise, high mortality.

Language: Английский

Citations

105

The Effects of Ventilation, Humidity, and Temperature on Bacterial Growth and Bacterial Genera Distribution DOI Open Access
Yujia Qiu, Yan Zhou, Yanfen Chang

et al.

International Journal of Environmental Research and Public Health, Journal Year: 2022, Volume and Issue: 19(22), P. 15345 - 15345

Published: Nov. 20, 2022

Bacteria are readily nourished in airtight environments with high humidity, such as storage cabinets, clothing closets, and corners, where ventilation is normally low humidity high.We characterized the role of bacterial growth genus distribution at different temperatures (26 °C 34 °C).Fresh pork, which was used substrate for culture, placed cabinets. Bacterial genera on surface pork a cabinet under °C); relative levels (RH: 50%, 70%, 90%); conditions (no low, medium, ventilation) were assessed by rDNA sequencing.Increased reduced significantly decreased 26 °C. The contribution increased to reduction exceeded that humidity. Ventilation had greatest effect reducing compared unventilated 70% RH. At °C, medium required reduce growth. High greatly growth, but could degree this increase.

Language: Английский

Citations

100

Antimicrobial Resistance Rates and Surveillance in Sub-Saharan Africa: Where Are We Now? DOI Creative Commons
Samuel Kariuki, Kelvin Kering,

Celestine Wairimu

et al.

Infection and Drug Resistance, Journal Year: 2022, Volume and Issue: Volume 15, P. 3589 - 3609

Published: July 1, 2022

Although antimicrobials have traditionally been used to treat infections and improve health outcomes, resistance commonly has posed a major challenge. An estimated 700,000 deaths occur globally every year as result of caused by antimicrobial-resistant pathogens. Antimicrobial (AMR) also contributes directly the decline in global economy. In 2019, sub-Saharan Africa (SSA) had highest mortality rate (23.5 per 100,000) attributable AMR compared other regions.We searched PubMed for articles relevant pathogens WHO-GLASS list local importance SSA. this review, we focused on rates surveillance these priority some most encountered public significance. addition, reviewed implementation national action plans mitigate against countries SSA.The SSA region is disproportionately affected AMR, part owing prevailing high levels poverty, which burden infectious diseases, poor regulation antimicrobial use, lack alternatives ineffective antimicrobials. The plan strategy prevention combating adopted countries, but fewer are able fully implement country-specific plans, several challenges exist many settings.A concerted One Health approach will be required ramp up region. addition surveillance, effective infection control, water, sanitation, hygiene, stewardship programs key cost-effective strategies helping tackle AMR.

Language: Английский

Citations

96

Selfish, promiscuous and sometimes useful: how mobile genetic elements drive horizontal gene transfer in microbial populations DOI Creative Commons
Matthieu Haudiquet, Jorge A. Moura de Sousa, Marie Touchon

et al.

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2022, Volume and Issue: 377(1861)

Published: Aug. 22, 2022

Horizontal gene transfer (HGT) drives microbial adaptation but is often under the control of mobile genetic elements (MGEs) whose interests are not necessarily aligned with those their hosts. In general, costly to donor cell while potentially beneficial recipients. The diversity and plasticity cell-MGEs interactions, among MGEs, result in complex evolutionary processes where source, or even existence selection for maintaining a function genome, unclear. For example, MGE-driven HGT depends on envelope structures defense systems, many these transferred by MGEs themselves. can spur periods intense increasing own rates horizontal transmission upon communicating, eavesdropping, sensing environment host physiology. This may high-frequency genes unrelated MGE. Here, we review how drive mechanisms, selective pressures genomic traits affect flow, therefore adaptation, populations. encoding adaptive niche-defining means that intragenomic conflicts alliances between cells key functional diversification. article part discussion meeting issue 'Genomic population pathogens'.

Language: Английский

Citations

88

A large-scale genomic snapshot of Klebsiella spp. isolates in Northern Italy reveals limited transmission between clinical and non-clinical settings DOI Creative Commons
Harry A. Thorpe,

Ross D. Booton,

Teemu Kallonen

et al.

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(12), P. 2054 - 2067

Published: Nov. 21, 2022

Abstract The Klebsiella group, found in humans, livestock, plants, soil, water and wild animals, is genetically ecologically diverse. Many species are opportunistic pathogens can harbour diverse classes of antimicrobial resistance genes. Healthcare-associated pneumoniae clones that non-susceptible to carbapenems spread rapidly, representing a high public health burden. Here we report an analysis 3,482 genome sequences 15 sampled over 17-month period from wide range clinical, community, animal environmental settings around the Italian city Pavia. Northern Italy hotspot for hospital-acquired carbapenem thus pertinent setting examine overlap between isolates clinical non-clinical settings. We no genotypic or phenotypic evidence non-susceptibility outside environment. Although noted occasional transmission settings, our data point limited role reservoirs human acquisition spp. also provide detailed genus-wide view genomic diversity population structure, including identification new groups.

Language: Английский

Citations

82

Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria DOI Creative Commons

Anusha Gauba,

Khondaker Miraz Rahman

Antibiotics, Journal Year: 2023, Volume and Issue: 12(11), P. 1590 - 1590

Published: Nov. 3, 2023

Multidrug-resistant Gram-negative bacterial infections are exponentially increasing, posing one of the most urgent global healthcare and economic threats. Due to lack new therapies, World Health Organization classified these species as priority pathogens in 2017, known ESKAPE pathogens. This classification emphasizes need for research development novel targeted therapies. The majority species, which possess a structurally dynamic cell envelope enabling them resist multiple antibiotics, thereby leading increased mortality rates. Despite 6 years having passed since WHO classification, progress generating treatment ideas has not been sufficient, antimicrobial resistance continues escalate, acting ticking time bomb. Numerous efforts strategies have employed combat rising levels antibiotic by targeting specific mechanisms. These mechanisms include inactivating/modifying enzymes, outer membrane porin remodelling, enhanced efflux pump action, alteration target sites. Some demonstrated clinical promise, such utilization beta-lactamase inhibitors adjuvants, well recent advancements machine-based learning employing artificial intelligence facilitate production narrow-spectrum antibiotics. However, further into an understanding precise occurs, specifically tailored each could pave way exploring review aims introduce key features bacteria their current approaches, summarizing major with focus on Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae. Additionally, potential directions alternative therapies will be discussed, along relative modes providing future perspective insight discipline resistance.

Language: Английский

Citations

76

Faecal microbiome-based machine learning for multi-class disease diagnosis DOI Creative Commons
Qi Su, Qin Liu, Raphaela Iris Lau

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 10, 2022

Abstract Systemic characterisation of the human faecal microbiome provides opportunity to develop non-invasive approaches in diagnosis a major disease. However, shared microbial signatures across different diseases make accurate challenging single-disease models. Herein, we present machine-learning multi-class model using metagenomic dataset 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, adenomas, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 species derived from 14.3 terabytes sequence. The trained achieves an area under receiver operating characteristic curve (AUROC) 0.90 0.99 (Interquartile range, IQR, 0.91–0.94) predicting independent test set, sensitivity 0.81 0.95 (IQR, 0.87–0.93) at specificity 0.76 0.98 (IQR 0.83–0.95). Metagenomic analysis public datasets 1,597 samples populations observes comparable predictions AUROC 0.69 0.91 0.79–0.87). Correlation top 50 disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease has potential clinical application diagnostics treatment response monitoring warrants further exploration.

Language: Английский

Citations

73

Bacterial extracellular vesicles: an emerging avenue to tackle diseases DOI
Junhua Xie, Freddy Haesebrouck, Lien Van Hoecke

et al.

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 31(12), P. 1206 - 1224

Published: June 16, 2023

Language: Английский

Citations

61

“Superbugs” with hypervirulence and carbapenem resistance in Klebsiella pneumoniae: the rise of such emerging nosocomial pathogens in China DOI Creative Commons

Danni Pu,

Jiankang Zhao, Kang Chang

et al.

Science Bulletin, Journal Year: 2023, Volume and Issue: 68(21), P. 2658 - 2670

Published: Sept. 30, 2023

Although hypervirulent Klebsiella pneumoniae (hvKP) can produce community-acquired infections that are fatal in young and adult hosts, such as pyogenic liver abscess, endophthalmitis, meningitis, it has historically been susceptible to antibiotics. Carbapenem-resistant K. (CRKP) is usually associated with urinary tract acquired hospitals, pneumonia, septicemias, soft tissue infections. Outbreaks quick spread of CRKP hospitals have become a major challenge public health due the lack effective antibacterial treatments. In early stages development, HvKP first appear distinct routes. However, lines dividing two pathotypes vanishing currently, advent carbapenem-resistant (CR-hvKP) devastating simultaneously multidrug-resistant, hypervirulent, highly transmissible. Most CR-hvKP cases reported Asian clinical settings, particularly China. Typically, develops when hvKP or acquires plasmids carry either carbapenem-resistance gene virulence gene. Alternatively, classic (cKP) may acquire hybrid plasmid carrying both genes. this review, we provide an overview key antimicrobial resistance mechanisms, factors, presentations, outcomes infection. Additionally, discuss possible evolutionary processes prevalence Given wide occurrence CR-hvKP, continued surveillance control measures organisms should be assigned higher priority.

Language: Английский

Citations

53