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Clinical Microbiology and Infection :... Sep 2023To analyse carbapenemases in Proteus mirabilis and assess the performance of carbapenemase detection assays.
OBJECTIVES
To analyse carbapenemases in Proteus mirabilis and assess the performance of carbapenemase detection assays.
METHODS
Eighty-one clinical P. mirabilis isolates with high-level resistance at least to ampicillin (>32 mg/L) or previous detection of carbapenemases were selected and investigated by three susceptibility testing methods (microdilution, automated susceptibility testing, and disk diffusion), six phenotypic carbapenemase assays (CARBA NP, modified carbapenemase inactivation method [CIM], modified zinc-supplemented CIM, simplified CIM, faropenem, and carbapenem-containing agar), two immunochromatographic assays, and whole-genome sequencing.
RESULTS
Carbapenemases were detected in 43 of 81 isolates (OXA-48-like [n = 13]; OXA-23 [n = 12]; OXA-58 [n = 12]; New Delhi metallo-β-lactamase (NDM) [n = 2]; Verona integron-encoded metallo-β-lactamase (VIM) [n = 2]; Imipenemase (IMP) [n = 1]; Klebsiella pneumoniae carbapenemase (KPC) [n = 1]). Carbapenemase-producing Proteus were frequently susceptible to ertapenem (26/43; 60%), meropenem (28/43; 65%), ceftazidime (33/43; 77%), and some even to piperacillin-tazobactam (9/43; 21%). Sensitivity/specificity of phenotypic tests were 30% (CI: 17-46%)/89% (CI: 75-97%) for CARBA NP, 74% (CI: 60-85%)/82% (CI: 67-91%) for faropenem, 91% (CI: 78-97%)/82% (CI: 66-92%) for simplified CIM, and 93% (CI: 81-99%)/100% (CI: 91-100%) for modified zinc-supplemented CIM. An algorithm for improved detection was developed, which demonstrated sensitivity/specificity of 100% (CI: 92-100%)/100% (CI: 91-100%) on the 81 isolates, and 100% (CI: 29-100%)/100% (CI: 96-100%) in a prospective analysis of additional 91 isolates. Interestingly, several OXA-23-producing isolates belonged to the same clonal lineage reported previously from France.
DISCUSSION
Current susceptibility testing methods and phenotypic tests frequently fail to detect carbapenemases in P. mirabilis, which could result in inadequate antibiotic treatment. In addition, the non-inclusion of bla in many molecular carbapenemase assays further impedes their detection. Therefore, the prevalence of carbapenemases in P. mirabilis is likely underestimated. With the herein proposed algorithm, carbapenemase-producing Proteus can be easily identified.
Topics: Humans; Proteus mirabilis; Bacterial Proteins; beta-Lactamases; Anti-Bacterial Agents; Algorithms; Zinc; Microbial Sensitivity Tests
PubMed: 37271195
DOI: 10.1016/j.cmi.2023.05.032 -
International Journal of Rheumatic... Mar 2024Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact cause of the disease is not yet fully understood, both environmental factors and genetics may play a role in its development. Moreover, research suggests microbiota contributes to the onset and progression of RA. People with RA show higher quantities of bacteria such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella copri, Proteus mirabilis, and Lactobacillus salivarius compared to healthy individuals. Conversely, studies propose that Lactobacillus casei, a probiotic bacterium with immunomodulatory properties, has beneficial effects for RA in murine and human models. Therefore, this work reviews the potential role of the gut microbiota in the development of RA and explores the feasibility of using probiotic bacteria as a supplementary treatment for this disease.
Topics: Humans; Mice; Animals; Microbiota; Arthritis, Rheumatoid; Gastrointestinal Microbiome; Inflammation; Probiotics
PubMed: 38487975
DOI: 10.1111/1756-185X.15122 -
Frontiers in Molecular Neuroscience 2023Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in...
INTRODUCTION
Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of ()-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis.
METHODS
We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect -induced disease progression and pathology.
RESULTS AND DISCUSSION
Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for -induced pathological progression and provides evidence of metabolic alterations associated with -mediated pathology of brain neurodegeneration.
PubMed: 37635904
DOI: 10.3389/fnmol.2023.1201073 -
International Journal of Molecular... Nov 2023, an opportunistic pathogen of the urinary tract, is known for its dimorphism and mobility. A connection of lipid alterations, induced by the rods elongation process,...
, an opportunistic pathogen of the urinary tract, is known for its dimorphism and mobility. A connection of lipid alterations, induced by the rods elongation process, with enhanced pathogenicity of long-form morphotype for the development of urinary tract infections, seems highly probable. Therefore, research on the adjustment in the composition and organization of lipids forming elongated rods was undertaken. The analyses performed using the ultra-high performance liquid chromatography with tandem mass spectrometry showed that drastic modifications in the morphology of rods that occur during the swarming process are directly related to deprivation of the long-form cells of PE 33:1 and PG 31:2 and their enrichment with PE 32:1, PE 34:1, PE 34:2, PG 30:2, PG 32:1, and PG 34:1. The analyses conducted by the gas chromatography-mass spectrometry showed negligible effects of the swarming process on fatty acids synthesis. However, the constant proportions between unsaturated and saturated fatty acids confirmed that phenotypic modifications in the rods induced by motility were independent of the saturation of the phospholipid tails. The method of the Förster resonance energy transfer revealed the influence of the swarming process on the melting of ordered lipid rafts present in the short-form rods, corresponding to the homogeneity of lipid bilayers in the long-form rods of . Confocal microscope photographs visualized strong Rhod-PE fluorescence of the whole area of swarmer cells, in contrast to weak membrane fluorescence of non-swarmer cells. It suggested an increased permeability of the bilayers in long-form rods morphologically adapted to the swarming process. These studies clearly demonstrate that swarming motility regulates the lipid composition and organization in rods.
Topics: Humans; Proteus mirabilis; Urinary Tract; Urinary Tract Infections; Chemical Phenomena; Lipids; Proteus Infections
PubMed: 38003652
DOI: 10.3390/ijms242216461 -
PloS One 2023Proteus mirabilis is an opportunistic pathogen associated with a variety of human infections, including urinary tract infections. The prevalence of P. mirabilis in foods...
Proteus mirabilis is an opportunistic pathogen associated with a variety of human infections, including urinary tract infections. The prevalence of P. mirabilis in foods of animal origin and in the manure by-products created in animal production is not well documented. Further, the prevalence and persistence of extended-spectrum cephalosporin (ESC) resistant P. mirabilis is largely unknown. In this study, we characterized ESC-resistant P. mirabilis recovered from various stages of dairy manure anaerobic digestion. Isolates were screened by PCR for blaCTX-M, blaCMY and blaSHV, and antimicrobial susceptibility testing was performed. Fifty-six P. mirabilis carrying CTX-M were sequenced with short and long read sequencing technologies, and the assembled chromosomes and plasmids were compared. ESC-resistant Proteus was found in four of the six manure digesters, an indication that not all digesters were colonized with resistant strains. Both CTX-M-1 and CTX-M-15 plasmids were found in P. mirabilis isolates. Transfer of plasmid DNA by conjugation was also explored, with ESC-resistance plasmids able to transfer to Escherichia coli at high frequency. We concluded that P. mirabilis can harbour and transfer ESC-resistance genes and plasmids, and may be an overlooked reservoir of antimicrobial resistance.
Topics: Animals; Cattle; Humans; Proteus mirabilis; Manure; Anaerobiosis; Cephalosporins; Escherichia coli; Plasmids; beta-Lactamases; Anti-Infective Agents; Anti-Bacterial Agents
PubMed: 37561682
DOI: 10.1371/journal.pone.0289703 -
Emerging Microbes & Infections Dec 2024OXA-48-like enzymes represent the most frequently detected carbapenemases in Enterobacterales in Western Europe, North Africa and the Middle East. In contrast to other...
OXA-48-like enzymes represent the most frequently detected carbapenemases in Enterobacterales in Western Europe, North Africa and the Middle East. In contrast to other species, the presence of OXA-48-like in leads to an unusually susceptible phenotype with low MICs for carbapenems and piperacillin-tazobactam, which is easily missed in the diagnostic laboratory. So far, there is little data available on the genetic environments of the corresponding genes, -like, in In this study susceptibility phenotypes and genomic data of 13 OXA-48-like-producing were investigated (OXA-48, = 9; OXA-181, = 3; OXA-162, = 1). Ten isolates were susceptible to meropenem and ertapenem and three isolates were susceptible to piperacillin-tazobactam. The gene was chromosomally located in 7/9 isolates. Thereof, in three isolates was inserted into a genomic island. Of the three isolates harbouring one was located on an IncX3 plasmid and two were located on a novel MOB plasmid, pOXA-P12, within the new transposon Tn. In 5/6 isolates with plasmidic location of like, the plasmids could conjugate to recipients . , -carrying plasmids could conjugate from other Enterobacterales into a recipient. These data show a high diversity of -like genetic environments compared to other Enterobacterales, where genetic environments are quite homogenous. Given the difficult-to-detect phenotype of OXA-48-like-producing and the location of -like on mobile genetic elements it is likely that OXA-48-like-producing can disseminate, escape most surveillance systems, and contribute to a hidden spread of OXA-48-like.
Topics: Proteus mirabilis; beta-Lactamases; Bacterial Proteins; Anti-Bacterial Agents; Microbial Sensitivity Tests; Humans; Proteus Infections; Plasmids; Genomic Islands; Carbapenems
PubMed: 38712879
DOI: 10.1080/22221751.2024.2353310 -
Journal of the Association of Medical... Sep 2023There is a paucity of studies investigating the population-based epidemiology of (MPP) group infections. Our objective was to determine the incidence, risk factors, and...
BACKGROUND
There is a paucity of studies investigating the population-based epidemiology of (MPP) group infections. Our objective was to determine the incidence, risk factors, and outcome of MPP group bloodstream infections (BSI), and explore species-specific differences.
METHODS
Population-based surveillance was conducted in the western interior of British Columbia, Canada, between April 1, 2010 and March 30, 2020.
RESULTS
Sixty-two incident MPP group BSI occurred for an annual incidence of 3.4 per 100,000 residents; rates for , , and species were 0.5, 2.6, and 0.3 per 100,000 population, respectively. The median year of age was 72.5 and was different ( = 0.03) among the groups. Most (92%) MPP group BSIs were of community-onset. Significant differences were observed in the distribution of clinical focus of infection, with most notably 81% of BSI due to genitourinary focus as compared to 60% and 22% for species and , respectively. Comorbid illnesses that increased the risk for development of MPP group BSI (incidence rate ratio; 95% CI) were HIV infection (37.0; 4.4-139.6), dementia (11.5; 6.1-20.7), cancer (6.4; 3.2-11.9), stroke 6.5 (2.8-13.3), and diabetes 2.7 (1.3-5.0). Thirteen, one, and none of the cases with , , and species BSI died within 30 days of index culture for respective all cause case-fatalities of 27%, 11%, and 0% ( = 0.1).
CONCLUSIONS
Although collectively responsible for a substantial burden of illness, the epidemiology of MPP group BSI varies significantly by species.
PubMed: 38250289
DOI: 10.3138/jammi-2022-0038 -
EBioMedicine Dec 2023Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the...
BACKGROUND
Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the gut-brain axis in central nervous system degeneration. Proteus mirabilis (P. mirabilis), a gram-negative facultative anaerobic bacterium, has been linked to brain neurodegeneration in animal studies. We hypothesised that P. mirabilis-derived virulence factors aggregate intestinal α-synuclein and could prompt the pathogenesis of dopaminergic neurodegeneration in the brain.
METHODS
We used vagotomised- and antibiotic-treated male murine models to determine the pathogenesis of P. mirabilis during brain neurodegeneration. The neurodegenerative factor that is driven by P. mirabilis was determined using genetically mutated P. mirabilis. The pathological functions and interactions of the virulence factors were determined in vitro.
FINDINGS
The results showed that P. mirabilis-induced motor dysfunction and neurodegeneration are regulated by intestinal α-syn aggregation in vagotomised- or antibiotic-treated murine models. We deduced that the specific virulence factor, haemolysin A (HpmA), plays a role in the pathogenesis of P. mirabilis. HpmA is involved in α-synuclein oligomerisation and membrane pore formation, resulting in the activation of mTOR-mediated autophagy signalling in intestinal neuroendocrine cells.
INTERPRETATION
Taken together, the results of the present study suggest that HpmA can interact with α-syn and act as a possible indicator of brain neurodegenerative diseases that are induced by P. mirabilis.
FUNDING
This study was supported by a grant from the National Research Foundation of Korea.
Topics: Animals; Male; Mice; alpha-Synuclein; Anti-Bacterial Agents; Base Composition; Hemolysin Proteins; Mirabilis; Phylogeny; Proteus mirabilis; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Virulence Factors
PubMed: 37995468
DOI: 10.1016/j.ebiom.2023.104887 -
Frontiers in Microbiology 2024is a Gram-negative bacterium with exclusive molecular and biological features. It is a versatile pathogen acclaimed for its distinct urease production, swarming... (Review)
Review
is a Gram-negative bacterium with exclusive molecular and biological features. It is a versatile pathogen acclaimed for its distinct urease production, swarming behavior, and rapid multicellular activity. Clinically, is a frequent pathogen of the human urinary system where it causes urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs). This review explores the epidemiology, risk factors, clinical manifestations, and treatment of infections, emphasizing its association with UTIs. The bacterium's genome analysis revealed the presence of resistance genes against commonly used antibiotics, an antibiotic-resistant phenotype that poses a serious clinical challenge. Particularly, the emergence of extended-spectrum β-lactamases (ESBLs) and carbapenemases resistant strains. On a molecular level, possesses a wide array of virulence factors including the production of fimbriae, urease, hemolysins, metallophores, and biofilm formation. This review thoroughly tackles a substantial gap in understanding the role of metallophores in shaping the virulence factors of virulence. Siderophores, iron metal chelating and transporting metallophores, particularly contribute to the complex pathogenic strategies, displaying a potential target for therapeutic intervention.
PubMed: 38646633
DOI: 10.3389/fmicb.2024.1383618 -
Soft Matter Oct 2023The twisting and writhing of a cell body and associated mechanical stresses is an underappreciated constraint on microbial self-propulsion. Multi-flagellated bacteria...
The twisting and writhing of a cell body and associated mechanical stresses is an underappreciated constraint on microbial self-propulsion. Multi-flagellated bacteria can even buckle and writhe under their own activity as they swim through a viscous fluid. New equilibrium configurations and steady-state dynamics then emerge which depend on the organism's mechanical properties and on the oriented distribution of flagella along its surface. Modeling the cell body as a semi-flexible Kirchhoff rod and coupling the mechanics to a flagellar orientation field, we derive the Euler-Poincaré equations governing the dynamics of the system, and rationalize experimental observations of buckling and writhing of elongated swarmer cells of the bacterium . A sequence of bifurcations is identified as the body is made more compliant, due to both buckling and torsional instabilities. These studies highlight a practical requirement for the stiffness of bacteria below which self-buckling occurs and cell motility becomes ineffective.
Topics: Bacteria; Flagella; Viscosity; Swimming
PubMed: 37740382
DOI: 10.1039/d3sm00572k