Article
Infectious Diseases
Yue Li, Yiwei Zhu, Wanqing Zhou, Zhongju Chen, Robert A. Moran, Huanhuan Ke, Yu Feng, Willem van Schaik, Han Shen, Jingshu Ji, Zhi Ruan, Xiaoting Hua, Yunsong Yu
Summary: This study characterized AFM-2 and AFM-3 metallo-beta-lactamase from clinical Pseudomonas aeruginosa isolates. The results showed that these enzymes exhibited beta-lactamase activity comparable to NDM-1, and the co-carriage of bla(AFM) and bla(KPC) genes rendered P. aeruginosa resistant to antipseudomonal beta-lactams. Furthermore, the association of bla(AFM) genes with translocatable genetic elements and plasmids highlighted their potential for dissemination.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Genetics & Heredity
Amy H. Y. Lee, William F. Porto, Celio de Faria, Simoni C. Dias, Sergio A. Alencar, Derek J. Pickard, Robert E. W. Hancock, Octavio L. Franco
Summary: The study sequenced 70 extensively drug resistant clinical isolates of Klebsiella pneumoniae from Brasilia's hospitals in Brazil, with majority belonging to a single clonal complex. Various resistance mechanisms were identified, with beta-lactamase production being the most notable association with the bacteria.
MICROBIAL GENOMICS
(2021)
Article
Microbiology
Andrea M. Hujer, Christopher R. Bethel, Magdalena A. Taracila, Steven H. Marshall, Laura J. Rojas, Marisa L. Winkler, Ronald E. Painter, T. Nicholas Domitrovic, Richard R. Watkins, Ayman M. Abdelhamed, Roshan D'Souza, Andrew R. Mack, Richard C. White, Thomas Clarke, Derrick E. Fouts, Michael R. Jacobs, Katherine Young, Robert A. Bonomo
Summary: Multidrug-resistant Pseudomonas aeruginosa infections pose a significant clinical challenge, especially when isolates exhibit resistance to carbapenems. This study identifies genetic factors, such as acquired beta-lactamases and disruptions in the OprD porin gene, that contribute to the resistance of two extensively drug-resistant P. aeruginosa isolates to imipenem-relebactam. Poor inhibition by relebactam of specific beta-lactamases within the isolates also contributes to the resistant phenotype.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Virology
Dragica Damnjanovic, Xabier Vazquez-Campos, Lisa Elliott, Mark Willcox, Wallace J. Bridge
Summary: This study investigated the infection capacity of Stenotrophomonas phage vB_SmaM_Ps15 on ocular S. maltophilia strains, finding that the phage had lytic activity and was resistant to multiple antibiotics and disinfectant solutions. Genomic analysis classified vB_SmaM_Ps15 as a new species of the Menderavirus genus, suggesting its potential use for treating S. maltophilia eye infections.
Article
Immunology
Pranita D. Tamma, Samuel L. Aitken, Robert A. Bonomo, Amy J. Mathers, David van Duin, Cornelius J. Clancy
Summary: The Infectious Diseases Society of America (IDSA) has provided updated guidance on the treatment of antimicrobial-resistant infections, focusing on treating AmpC-producing Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia infections. The guidance is based on clinical experience, expert opinion, and a review of available literature, as published data on optimal treatment options are limited. This document emphasizes treatment approaches for infections in the United States, considering differences in resistance epidemiology and the availability of specific anti-infectives internationally.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
ChengCheng Yue, WeiHua Shen, LiFen Hu, YanYan Liu, YaHong Zheng, Ying Ye, Yuhao Zhang, JiaBin Li
Summary: The study demonstrated that the combination of azithromycin and tigecycline effectively inhibited biofilm formation by S. maltophilia. Specifically, the combination of 2x MIC azithromycin with 1x MIC tigecycline showed the best inhibitory effect, significantly reducing biofilm thickness.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Environmental Sciences
Shuhong Zhang, Guangli Yang, Yali Jiang
Summary: Whole-genome sequencing of Stenotrophomonas maltophilia from permafrost revealed lower maximum minimum inhibitory concentration (MIC) of antibiotics and metals, as well as fewer antibiotic resistance genes and metal resistance genes compared to clinical strains. This suggests that the occurrence of antibiotic and metal resistance in permafrost strains is due to inherent resistance rather than human-induced selective pressure.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Microbiology
Arianna Pompilio, Marco Ranalli, Alessandra Piccirilli, Mariagrazia Perilli, Dragana Vukovic, Branislava Savic, Marcela Krutova, Pavel Drevinek, Daniel Jonas, Ersilia V. Fiscarelli, Vanessa Tuccio Guarna Assanti, Maria M. Tavio, Fernando Artiles, Giovanni Di Bonaventura
Summary: The ability of Stenotrophomonas maltophilia to form biofilms is a significant factor in the pathogenesis of infections, especially in deep infections. Biofilm formation is positively correlated with clinical outcomes such as mechanical ventilation, and negatively correlated with antibiotic resistance, particularly in pathogenic strains. Mature biofilms of S. maltophilia are much more resistant to antibiotics compared to planktonic cells, especially in the case of bloodborne strains. Additional studies with larger patient cohorts and isolates are warranted to further investigate this phenomenon.
Article
Biochemistry & Molecular Biology
K. H. Sreenithya, Dhananjay Jade, Michael A. Harrison, Shobana Sugumar
Summary: Antibiotic resistance poses a significant threat to the medical industry in treating microbial infections. Gram-negative organisms are developing multi-drug resistance, making commonly used drugs ineffective. The World Health Organization has called for the development of new strategies and novel compounds to address this issue. Plant secondary metabolites, with their antimicrobial properties and long history of traditional medicinal use, hold potential for combating drug-resistant organisms. Computational technologies can aid in identifying the best inhibitors, improving treatment outcomes.
JOURNAL OF MOLECULAR MODELING
(2022)
Article
Microbiology
Yahao Li, Mingfang Pu, Pengjun Han, Mengzhe Li, Xiaoping An, Lihua Song, Huahao Fan, Zeliang Chen, Yigang Tong
Summary: In recent years, Stenotrophomonas maltophilia has become an important and highly pathogenic pathogen in clinically acquired infections. Additionally, multidrug-resistant S. maltophilia infections have become a serious challenge. Bacteriophages, with their unique antibacterial mechanism and superior bactericidal ability, offer a promising alternative for the treatment of these infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Akram Azimi, Farhad Rezaei, Mehdi Yaseri, Sirus Jafari, Mohammad Rahbar, Masoumeh Douraghi
Summary: Stenotrophomonas maltophilia demonstrates a wide spectrum of fluoroquinolone resistance through various mechanisms such as multidrug efflux pumps and Smqnr alleles. The presence of efflux pumps like SmeDEF, SmeVWX and Smqnr genes significantly contribute to fluoroquinolone resistance. Smqnr8 is the most common allele found in ciprofloxacin-resistant isolates, indicating a role in low-level levofloxacin resistance.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Megan Y. Nas, Jeffrey Gabell, Nicholas P. Cianciotto
Summary: Previously, it was found that Stenotrophomonas maltophilia possesses a T4SS that can kill other bacteria, with two effectors, RS14245 and RS14255, identified as key components in killing pathogenic Pseudomonas aeruginosa. These findings represent a significant advancement in understanding S. maltophilia, T4SS function, clinically relevant interactions, and bactericidal activities.
Article
Infectious Diseases
Patchrapa Boonmee, Worapong Nasomsong, Narisorn Lorchirachoonkul, Supanun Pungcharoenkijkul, Piraporn Juntanawiwat, Suphatthra Chaemchaeng, Wichai Santimaleeworagun
Summary: This retrospective study examined the antimicrobial susceptibility profile and clinical outcomes of S. maltophilia infections at three tertiary care hospitals in Central Thailand. The results showed a high mortality rate and identified severity of illness and non-use of TMP-SMX as predictive factors for treatment failure. A TMP-SMX-based regimen was recommended for the treatment of S. maltophilia infections.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Chemistry, Physical
Rozina Tabassum, Ghulam Abbas, Syed Sikander Azam
Summary: This study designed a multi-epitope vaccine against S. maltophilia using an integrative computational strategy, identified potential antigenic membrane proteins through subtractive proteomics and immunoinformatics analysis, designed vaccine construct by stitching preferred peptides, validated the docked pose of construct-TLR4 complex, and explored its dynamic behavior through molecular dynamics simulations. The immune simulations predicted robust immune responses, indicating the potential of this designed vaccine as a protective antigen against S. maltophilia.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Infectious Diseases
Linlin Xie, Aiping Zhou, Jia Zhao, Yuhang Tang, Rui Zhao, Yingping Zhou, Guangxiang Cao, Chuanqing Zhong, Jun Li
Summary: The study identified the genetic determinants contributing to multidrug resistance in Stenotrophomonas maltophilia strain MER1 isolated from hospital wastewater in Shandong Province, China. The strain showed resistance to multiple antibiotics and harbored genes encoding efflux pumps and drug-inactivating agents. The findings highlight the risk of spread of multidrug resistance genes in S. maltophilia to various ecological niches or medically high-risk pathogens.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2021)
Article
Biochemistry & Molecular Biology
Silvia Gervasoni, James Spencer, Philip Hinchliffe, Alessandro Pedretti, Franco Vairoletti, Graciela Mahler, Adrian J. Mulholland
Summary: This study presents a multiscale approach to model thiol inhibitor binding to IMP-1, demonstrating a reliable computational pipeline that can be applied to inhibitor design for MBLs and other zinc-metalloenzyme systems. The workflow involves molecular simulations, molecular dynamics simulations, QM/MM optimization, and the use of density functional theory to increase the accuracy of predictions. The limitations of empirical models for treating these systems are highlighted, suggesting the need for higher level calculations for reliable structural predictions.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Biotechnology & Applied Microbiology
Andrea Turner, Hannah Schubert, Emma F. Puddy, Jordan E. Sealey, Virginia C. Gould, Tristan A. Cogan, Matthew B. Avison, Kristen K. Reyher
Summary: Sampling methodology and sample handling have a greater association than on-farm factors with the detection of ABR E. coli in individual faecal samples from dairy heifers.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Lewis D. Turner, Chi H. Trinh, Ryan A. Hubball, Kyle M. Orritt, Chi-Chuan Lin, Julie E. Burns, Margaret A. Knowles, Colin W. G. Fishwick
Summary: This study describes a structure-guided approach to design a selective FGFR2 inhibitor, resulting in a nanomolar potency inhibitor with moderate selectivity for FGFR2. The study reveals that inhibitor-specific morphological differences may play a crucial role in selectivity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jurgen Brem, Tharindi Panduwawala, Jon Ulf Hansen, Joanne Hewitt, Edgars Liepins, Pawel Donets, Laura Espina, Alistair J. M. Farley, Kirill Shubin, Gonzalo Gomez Campillos, Paula Kiuru, Shifali Shishodia, Daniel Krahn, Robert K. Lesniak, Juliane Schmidt (Adrian), Karina Calvopina, Maria-Carmen Turrientes, Madeline E. Kavanagh, Dmitrijs Lubriks, Philip Hinchliffe, Gareth W. Langley, Ali F. Aboklaish, Anders Eneroth, Maria Backlund, Andrei G. Baran, Elisabet Nielsen, Michael Speake, Janis Kuka, John Robinson, Solveiga Grinberga, Lindsay Robinson, Michael A. McDonough, Anna M. Rydzik, Thomas M. Leissing, Juan Carlos Jimenez-Castellanos, Matthew B. Avison, Solange Da Silva Pinto, Andrew D. Pannifer, Marina Martjuga, Emma Widlake, Martins Priede, Iva Hopkins Navratilova, Marek Gniadkowski, Anna Karin Belfrage, Peter Brandt, Jari Yli-Kauhaluoma, Eric Bacque, Malcolm G. P. Page, Fredrik Bjorkling, Jonathan M. Tyrrell, James Spencer, Pauline A. Lang, Pawel Baranczewski, Rafael Canton, Stuart P. McElroy, Philip S. Jones, Fernando Baquero, Edgars Suna, Angus Morrison, Timothy R. Walsh, Christopher J. Schofield
Summary: The discovery of a potent new class of MBL inhibitor, InCs, restores carbapenem activity against multidrug-resistant bacteria with low resistance frequency. In combination with meropenem, InCs show strong in vivo efficacy in mouse infection models.
Article
Medicine, Research & Experimental
Natalia Drabinska, Keith Hewett, Paul White, Matthew B. Avison, Raj Persad, Norman M. Ratcliffe, Ben de Lacy Costello
Summary: The study demonstrates the potential of VOC analysis using a GC-MS/MOS system for early detection of CTX-M-producing, antibiotic-resistant E. coli responsible for UTIs. Significant effects were observed for MOS signals and two-way interactions, indicating the ability to distinguish bacteria within 2 hours after antibiotic addition.
ADVANCES IN MEDICAL SCIENCES
(2022)
Article
Microbiology
Naphat Satapoomin, Punyawee Dulyayangkul, Matthew B. Avison
Summary: The study reveals a variant of Klebsiella pneumoniae that exhibits resistance to multiple antibiotics, including ceftazidime-avibactam and meropenem-vaborbactam. Further mutations and enzyme production are required for resistance to other antibiotics.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Philip Hinchliffe, Catherine L. Tooke, Christopher R. Bethel, Benlian Wang, Christopher Arthur, Kate J. Heesom, Stuart Shapiro, Daniela M. Schlatzer, Krisztina M. Papp-Wallace, Robert A. Bonomo, James Spencer
Summary: This study reveals the mechanism of action of two β-lactamase inhibitors, enmetazobactam and tazobactam, on CTX-M-15 β-lactamase in Escherichia coli, including the formation of protein cross-link and epimerization of amino acids.
Article
Infectious Diseases
Anka Lucic, Tika R. Malla, Karina Calvopina, Catherine L. Tooke, Jurgen Brem, Michael A. McDonough, James Spencer, Christopher J. Schofield
Summary: This study investigated the reaction of the carbapenem biapenem with different subclasses of beta-lactamases. The results showed the formation of enamine and various types of imine products. The findings support the idea that prolonging the lifetime of beta-lactamase carbapenem complexes by optimizing the tautomerization process could lead to improved carbapenems.
Article
Public, Environmental & Occupational Health
Oliver Mounsey, Kezia Wareham, Ashley Hammond, Jacqueline Findlay, Virginia C. Gould, Katy Morley, Tristan A. Cogan, Katy M. E. Turner, Matthew B. Avison, Kristen K. Reyher
Summary: This study investigated the carriage of antibacterial resistant Escherichia coli in 16-week-old dogs in the UK. The results showed that raw feeding was associated with the presence of resistant bacteria, and that the bacteria carried by puppies were shared with humans. This suggests that raw feeding may contribute to the transmission of antibacterial resistant bacteria.
Article
Infectious Diseases
Jordan E. Sealey, Ashley Hammond, Oliver Mounsey, Virginia C. Gould, Kristen K. Reyher, Matthew B. Avison
Summary: This study compares faecal third-generation cephalosporin-resistant (3GC-R) Escherichia coli isolates from dogs living in a city and a rural area, and also compares isolates from dogs, cattle, and humans in these regions. Risk factors associated with 3GC-R E. coli carriage in dogs were determined. The results indicate that in rural dogs, carriage of 3GC-R E. coli, particularly CTX-M producers, is phylogenetically associated with interaction with local cattle and epidemiologically associated with feeding raw meat. In urban dogs, sources of 3GC-R E. coli appear to be more varied and include environments such as rivers.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Philip Hinchliffe, Karina Calvopina, Patrick Rabe, Maria F. Mojica, Christopher J. Schofiled, Gary I. Dmitrienko, Robert A. Bonomo, Alejandro J. Vila, James Spencer
Summary: L1 is a dizinc subclass B3 metallo-beta-lactamase that plays a key role in antibiotic resistance in Stenotrophomonas maltophilia. It hydrolyzes beta-lactam antibiotics and is resistant to current MBL inhibitors. This study provides insights into the structure and mechanism of L1 through kinetic studies and crystal structures, offering potential for the development of new antibiotics and inhibitors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Cheng Chen, Yinsui Xu, Peter Oelschlaeger, Juergen Brem, Lu Liu, Dongmei Wang, Hongzhe Sun, Ke-Wu Yang
Summary: The emergence of multi-drug resistant pathogens co-expressing serine and metallo-carbapenemases significantly reduces the effectiveness of carbapenems. The first SeCN-derived dual inhibitor of serine and metallo-carbapenemases is reported, with IC50 values ranging from 0.0038 to 1.27 & mu;g mL(-1). The inhibitor forms covalent bonds with Cys221 of NDM-1 and Ser70 of KPC-2, achieving selective labelling and cross-class inhibition for carbapenemases. These findings provide a potential strategy to develop clinically useful dual inhibitors targeting serine and metallo-carbapenemases to combat superbugs.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Mariska de Munnik, Pauline A. A. Lang, Francisco De Dios Anton, Monica Cacho, Robert H. Bates, Jurgen Brem, Beatriz Rodriguez Miquel, Christopher J. Schofield
Summary: Disrupting bacterial cell wall biosynthesis in Mycobacterium tuberculosis is a promising approach for treating tuberculosis. In this study, a high-throughput assay was used to identify potent inhibitors of L,D-transpeptidase Ldt(Mt2), which plays an essential role in the formation of cell wall peptidoglycan. These inhibitors were found to react covalently with the catalytic cysteine of Ldt(Mt2) and showed bactericidal effects on M. tuberculosis.