Explore the vast range of titles available.

(Pr) and (Ps) are clinically relevant opportunistic pathogens. They are resistant to several antibiotics including carbapenems. The immune response against these pathogens has never been investigated. Here, we aimed to evaluate whether neutrophils (PMN), key players against bacterial infections, were able to recognize and eliminate these bacteria. We measured PMN functions after challenge with selected clinical isolates of Pr and Ps, and used ATCC (Eco), which fully activates PMN, for comparison. Bacterial survival was evaluated after exposure of PMN to bacteria for 1 or 3 h and colony formation units (CFU) were determined. While PMN were able to partially contain Ps growth at 1 h, at 3 h both Pr and Ps were able to escape PMN-mediated killing compared to Eco, which was efficiently killed. Reactive oxygen species (ROS) generation was not induced by Pr or poorly induced by Ps, compared to Eco, but phagocytosis of Pr, Ps, and Eco was similar. Although Pr and Ps induced the release of double-stranded (d.s.) DNA early at 30 min (vital neutrophils extracellular traps or NETs), the release of late-induced NETs (3 h, suicidal NETs) was not observed, consistent with the absence of PMN death observed with Pr or Ps. In addition, Pr and Ps decreased suicidal NETs when Eco or PMA were used as inducers. This decrease was abolished by fixed bacteria, and was dependent on the release of a DNase activity. Twenty-four h after i.p. inoculation of mice with Pr, Ps or Eco, all bacteria induced migration of PMN to the peritoneum, but no PMN activation or NETs was observed in Pr or Ps-treated mice. When the distribution of bacteria in different organs was measured by CFU determination, Pr and Ps disseminated to the spleen and lungs, whereas Eco was exclusively present in the peritoneum. The isolates used in this study of Pr and Ps are poor inducers of bactericidal PMN responses and display immune evasion strategies to subvert PMN-mediated killing. These evasion mechanisms, acting on degrading vital NETs and/or blocking the formation of suicidal NETs, would favor bacterial dissemination.

The increasing antimicrobial resistance in Providencia stuartii ( P. stuartii ) worldwide, particularly concerning for immunocompromised and burn patients, has raised concern in Bangladesh, where the significance of this infectious opportunistic pathogen had been previously overlooked, prompting a need for investigation . The two strains of P. stuartii ( P. stuartii SHNIBPS63 and P. stuartii SHNIBPS71) isolated from wound swab of two critically injured burn patients were found to be multidrug-resistant and P. stuartii SHNIBPS63 showed resistance to all the 22 antibiotics tested as well as revealed the co-existence of bla VEB-6 (Class A), bla NDM-1 (Class B), bla OXA-10 (Class D) beta lactamase genes. Complete resistance to carbapenems through the production of NDM-1, is indicative of an alarming situation as carbapenems are considered to be the last line antibiotic to combat this pathogen. Both isolates displayed strong biofilm-forming abilities and exhibited resistance to copper, zinc, and iron, in addition to carrying multiple genes associated with metal resistance and the formation of biofilms. The study also encompassed a pangenome analysis utilizing a dataset of eighty-six publicly available P. stuartii genomes (n = 86), revealing evidence of an open or expanding pangenome for P. stuartii . Also, an extensive genome-wide analysis of all the P. stuartii genomes revealed a concerning global prevalence of diverse antimicrobial resistance genes, with a particular alarm raised over the abundance of carbapenem resistance gene bla NDM-1 . Additionally, this study highlighted the notable genetic diversity within P. stuartii , significant informations about phylogenomic relationships and ancestry, as well as potential for cross-species transmission, raising important implications for public health and microbial adaptation across different environments.

Providencia stuartii is an emerging pathogen that causes nosocomial infections. In this study, a multidrug-resistant strain P. stuartii MF1 was isolated from swine wastewater. Comprehensive analysis of whole genome sequencing revealed that dozens of antibiotic resistance genes were found in MF1. A novel transposon Tn 6450M which has high sequence identity to Tn 6450 and the plasmid-borne Tn 6765 from Proteus mirabilis was identified in the genome of MF1 . Tn 6450M was determined to be stably inserted into a new att Tn7 site in the P. stuartii MF1 genome and contains the third-generation cephalosporins resistance-associated genes blaDHA-1 . Intergeneric transmission of Tn 6450 variants poses risks for the spread of antibiotic resistance genes.

Background As a pervasive insect that transmits a variety of pathogens to humans and animals, the housefly has abundant and diverse microbial communities in its intestines. These gut microbes play an important role in the biology of insects and form a symbiotic relationship with the host insect. Alterations in the structure of the gut microbial community would affect larval development. Therefore, it is important to understand the mechanism regulating the influence of specific bacteria on the development of housefly larvae. Methods For this study we selected the intestinal symbiotic bacterium Enterobacter hormaechei , which is beneficial to the growth and development of housefly larvae, and used it as a probiotic supplement in larval feed. 16S rRNA gene sequencing technology was used to explore the effect of E. hormaechei  on the intestinal flora of housefly larvae, and plate confrontation experiments were performed to study the interaction between E. hormaechei and intestinal microorganisms. Results The composition of the gut microflora of the larvae changed after the larvae were fed E. hormaechei , with the abundance of Pseudochrobactrum ,  Enterobacter and Vagococcus  increasing and that of Klebsiella  and  Bacillus decreasing. Analysis of the structure and interaction of larval intestinal flora revealed that E. hormaechei inhibited the growth of harmful bacteria, such as Pseudomonas aeruginosa , Providencia stuartii and Providencia vermicola , and promoted the reproduction of beneficial bacteria. Conclusions Our study has explored the influence of specific beneficial bacteria on the intestinal flora of houseflies. The results of this study reveal the important role played by specific beneficial bacteria on the development of housefly larvae and provide insight for the development of sustained biological agents for housefly control through interference of gut microbiota. Graphical abstract

Nitin Kumar,1 Harit Kumar2 1Department of Microbiology, Symbiosis Medical College for Women, Symbiosis International (Deemed University), Lavale, Pune, Maharashtra, India; 2Department of Microbiology, Maharishi Markandeshwar Institute of Medical Science & Research, Maharishi Markandeshwar (Deemed to be) University, Mullana, Mullana, Haryana, IndiaCorrespondence: Harit Kumar, Department of Microbiology, Maharishi Markandeshwar Institute of Medical Science & Research, Maharishi Markandeshwar (Deemed to be) University Mullana, Haryana, India, Email kumarharit4@gmail.com View the original paper by Mr Woreta and colleaguesA Response to Letter has been published for this article.

Objectives To investigate the clinical and drug resistance characteristics of Providencia stuartii infections in the Huainan region of Anhui and provide a reference for the clinical selection of antimicrobial agents. Methods This single-center retrospective analysis included 76 patients with P. stuartii infection in Huainan during the period from October 2018 to March 2020. The hospital department in which the patients were treated and the drug susceptibility characteristics of the P. stuartii isolates were recorded. Results Among the 76 patients, the lung was the most common site of infection, and intensive care unit was the main hospital department. Extended spectrum beta-lactamase screening revealed expression by all 76 isolates of P. stuartii. Of the 76 isolates, 92.1% exhibited multiple drug resistance or extensive drug resistance. P. stuartii isolates were sensitive to cefepime and imipenem, but not to other beta-lactam antibiotics. Twenty isolates were resistant to all 21 types of antibiotics. Of the 20 patients infected with extensively drug-resistant isolates, nine (45%) died. Conclusions Drug resistance is increasing in P. stuartii. The antimicrobial agent imipenem may be effective for treatment of P. stuartii infections. Fluoroquinolones, aminoglycosides, and fourth-generation cephalosporins are suitable options for antibiotic therapy.

Background/objectives: A rise in infections associated with carbapenem-resistant Providencia species (CRPS) has been observed worldwide. This study presents a genomic analysis of CRPS isolates from four hospitals in Croatia and the outpatient setting, in order to determine the extent of the spread of CRPS in Croatia. In the present study, we applied a combination of phenotypic characterization and molecular analysis of resistance traits to determine the mechanisms and the routes of spread of CRPS. Material and methods: The antibiotic susceptibility testing was performed using disk-diffusion and broth dilution methods. The nature of extended-spectrum β-lactamases (ESBLs), carbapenemases, and fluoroquinolone resistance determinants was investigated by polymerase chain reaction (PCR). In order to obtain an insight into the whole resistome, selected isolates were subjected to the Interarray Genotyping Kit CarbaResist and whole genome sequencing (WGS). Results: In total, 30 isolates were collected from four centers, located in different geographic regions of Croatia. There was uniform resistance to piperacillin-tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESCs), imipenem, ertapenem, meropenem, and ciprofloxacin. Immunochromatographic testing and PCR revealed OXA-48 and NDM carbapenemase in 15 isolates, respectively. Phenotypic tests for ESBLs were positive in all OXA-48 and one NDM-positive organism (16 isolates). The isolates were categorized as extensively drug-resistant (XDR). OXA-48-producing isolates were susceptible only to ceftazidime-avibactam, whereas NDM producers were susceptible to cefiderocol and, in the majority of cases, also to amikacin. WGS identified a plethora of genes encoding resistance to aminoglycosides, such as aadA1 and aadA2, (aph(3″)-Ib and aph(6)-Id, sulfonamides sul1 and sul2, trimethoprim dfrA1, dfrA10, and dfrA12, tetracyclines tet(A) and tet(B), and chloramphenicol catA3 and catA5. Conclusions: Providencia spp., in spite of being a rare pathogen, should be included in the surveillance studies across the medical centers in Croatia.

Background. Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally. Methods. A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity. Results. Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture. Conclusions. We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI.

Background: The present study investigates the potential bioactivity of twelve experimentally designed C-2 quaternary indolinones against Providencia spp., a bacterial group of the Enterobacteriaceae family known to cause urinary tract infections. The study aims to provide insights into the bioactive properties of the investigated compounds and their potential use in developing novel treatments against Providencia spp. The experimental design of indolinones, combined with their unique chemical structure, makes them attractive candidates for further investigation. The results of this research may contribute to the development of novel therapeutic agents to combat Providencia spp. infections. Methods: The synthesized indolinones (moLl-moL12) are evaluated to identify any superior activity, particularly focusing on moL12, which possesses aza functionality. The antimicrobial activities of all twelve compounds are tested in triplicates against six different Gram-positive and Gram-negative organisms, including P. vermicola (P<0.05). Computational methods have been employed to assess the pharmacokinetic properties of the compounds. Results: Among the synthesized indolinones, moL12 exhibits superior activity compared to the other compounds with similar skeleton but different functional moieties. All six strains tested, including P. vermicola, demonstrated sensitivity to moL12. Computational studies support the pharmacokinetic properties of moL12, indicating acceptable absorption, distribution, metabolism, excretion, and toxicity characteristics. Conclusion: Utilizing the PPI approach, we have identified a promising target, FabD, in Gram-negative bacteria. Our analysis has shown that moL12 exhibits significant potential in binding with FabD, thereby, might inhibit cell wall formation, and display superior antimicrobial activity compared to other compounds. Consequently, moL12 may be a potential therapeutic agent that could be used to combat urinary tract infections caused by Providencia spp. The findings of this research hold significant promise for the development of new and effective treatments for bacterial infections. Keywords: C-2 quaternary indolinones, Providencia vermicola, Providencia stuartii, multi-drug resistance, molecular docking, molecular dynamics simulation

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp., and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole-genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36), and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii, and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 were observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates we observed highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening infection control measures.