Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Differential Contribution of Hydrogen Metabolism to Proteus mirabilis Fitness during Single-Species and Polymicrobial Catheterized Urinary Tract Infection.

Proteus mirabilis is a common uropathogen and a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Through a genome-wide screen, we previously identified two [NiFe] hydrogenases as candidate fitness factors for P. mirabilis CAUTI: a Hyb-type Group 1c H2-uptake hydrogenase and a Hyf-type Group 4a H2-producing hydrogenase. In this study, we disrupted one gene of each system (hyfE and hybC) and also generated a double mutant to examine the contribution of flexible H2 metabolism to P. mirabilis growth and fitness in vitro and during experimental CAUTI. Since P. mirabilis is typically present as part of a polymicrobial community in the urinary tract, we also examined the impact of two common co-colonization partners, Providencia stuartii and Enterococcus faecalis, on the expression and contribution of each hydrogenase to fitness. Our data demonstrate that neither system alone is critical for P. mirabilis growth in vitro or fitness during experimental CAUTI. However, perturbation of flexible H2 metabolism in the ∆hybC∆hyfE double mutant decreased P. mirabilis fitness in vitro and during infection. The Hyf system alone contributed to the generation of proton motive force and swarming motility, but only during anaerobic conditions. Unexpectedly, both systems contributed to benzyl viologen reduction in TYET medium, and disruption of either system increased expression of the other. We further demonstrate that polymicrobial interactions with P. stuartii and E. faecalis alter the expression of Hyb and Hyf in vitro as well as the contribution of each system to P. mirabilis fitness during CAUTI.

An Integrative Approach to Study the Inhibition of Providencia vermicola FabD Using C2-Quaternary Indolinones.

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 (moL1-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.

Genotypic Evolution of Klebsiella pneumoniae Sequence Type 512 during Ceftazidime/Avibactam, Meropenem/Vaborbactam, and Cefiderocol Treatment, Italy.

In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2 in the intensive care unit of Policlinico Umberto I hospital in Rome, Italy. During 95 days of hospitalization, ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol were administered consecutively to treat 3 respiratory tract infections sustained by different bacterial agents. Those therapies altered the resistome of K. pneumoniae sequence type 512 colonizing or infecting the patient during the hospitalization period. In vivo evolution of the K. pneumoniae sequence type 512 resistome occurred through plasmid loss, outer membrane porin alteration, and a nonsense mutation in the cirA siderophore gene, resulting in high levels of cefiderocol resistance. Cross-selection can occur between K. pneumoniae and treatments prescribed for other infective agents. K. pneumoniae can stably colonize a patient, and antimicrobial-selective pressure can promote progressive K. pneumoniae resistome evolution, indicating a substantial public health threat.

Genome-Based Retrospective Analysis of a Providencia stuartii Outbreak in Rome, Italy: Broad Spectrum IncC Plasmids Spread the NDM Carbapenemase within the Hospital.

Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Whole-genome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the blaNDM-1 metallo-ß-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most ß-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment.

AadA36, a novel chromosomal aminoglycoside nucleotidyltransferase from a clinical isolate of Providencia stuartii.

In this study, we characterized a novel chromosome-encoded aminoglycoside nucleotidyltransferase (ANT), AadA36, from the Providencia stuartii strain P14 isolated from the sputum specimen of a burn patient at a hospital in Wenzhou, China. Among the functionally characterized ANTs, AadA36 shared the highest amino acid sequence identity of 51.91% with AadA14. The whole genome of P. stuartii P14 consisted of one chromosome and two plasmids (designated pP14-166 and pP14-114). A total of 19 genes with ≥80% similarity with functionally characterized antimicrobial resistance genes (ARGs) were identified in the whole genome, including aminoglycosides [aac(2')-Ia, aph(6)-Id, aph(3″)-Ib, aac(6')-Ib, ant(3″)-IIa, aph(3')-Ia], ß-lactams (bla CMY-2 and bla OXA-10) and so on. Antimicrobial susceptibility testing showed that the aadA36 gene conferred specific resistance to spectinomycin and streptomycin, and the minimum inhibitory concentration (MIC) of these antimicrobials increased 128- and 64-fold compared with the control strain. The kinetic parameters of AadA36 were consistent with the MIC data of spectinomycin and streptomycin, with kcat /Km ratios of (1.07 ± 2.23) × 104 M-1 s-1 and (8.96 ± 1.01) × 103 M-1 s-1, respectively. The identification of a novel aminoglycoside resistance gene will help us further understand the complexity of the resistance mechanisms and provide deep insights into the dissemination of resistance genes in the microbial population.

Socialization of Providencia stuartii Enables Resistance to Environmental Insults.

Providencia stuartii is a highly social pathogen responsible for nosocomial chronic urinary tract infections. The bacterium indeed forms floating communities of cells (FCC) besides and prior-to canonical surface-attached biofilms (SAB). Within P. stuartii FCC, cells are riveted one to another owing to by self-interactions between its porins, viz. Omp-Pst1 and Omp-Pst2. In pathophysiological conditions, P. stuartii is principally exposed to high concentrations of urea, ammonia, bicarbonate, creatinine and to large variations of pH, questioning how these environmental cues affect socialization, and whether formation of SAB and FCC protects cells against those. Results from our investigations indicate that FCC and SAB can both form in the urinary tract, endowing cells with increased resistance and fitness. They additionally show that while Omp-Pst1 is the main gateway allowing penetration of urea, bicarbonate and ammonia into the periplasm, expression of Omp-Pst2 enables resistance to them.

Immobilization of Providencia stuartii Cells in Pumice Stone and Its Application for N-Acetylglucosamine Production.

Research background: Shrimp shells contain chitin that can be further processed into N-acetylglucosamine, which has been extensively used to treat joint damage. Providencia stuartii has a strong chitinolytic activity and may be utilized in the form of immobilized cells in repeated fermentation. Pumice is a porous and rigid stone that offers superior mechanical strength, making it suitable for immobilization. Experimental approach: In the research submerged fermentation with different pumice stone sizes and pumice stone/growth medium ratios (m/V) was carried out for 4 days at 37 °C and pH=7.0. The optimum pumice stone size and pumice stone/growth medium ratio (m/V) were used to determine the optimum fermentation cycle for the production of N-acetylglucosamine using immobilized P. stuartii. Results and conclusions: Pumice stones of 1.0 cm×1.0 cm×1.0 cm and pumice stone/growth medium ratio of 1:5 were found to be the optimum conditions for successful immobilization of (90.0±1.6) % cells and production of (331.4±7.3) g/L N-acetylglucosamine. The highest N-acetylglucosamine concentration of (323.0±2.5) g/L was obtained in the first fermentation cycle, which then decreased and remained stable throughout the last three cycles. Novelty and scientific contribution: P. stuartii, a strong chitinolytic bacterium previously isolated from rotten shrimp shells, was used for the first time in immobilized form to produce N-acetylglucosamine. The findings in this research showed the potential use of P. stuartii cells immobilized in pumice stone for continuous production of N-acetylglucosamine in repeated fermentation.

Targeting Biofilm of MDR Providencia stuartii by Phages Using a Catheter Model.

Providencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and temperate bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.

First report of the aac(6)-Ib-cr gene in Providencia stuartii isolates in Brazil

Abstract INTRODUCTION: The aac(6')-Ib-cr and bla KPC genes are spreading among Enterobacteriaceae species, including Providencia stuartii, in some countries of world. METHODS: These genes were investigated in 28 P. stuartii isolates from a public hospital in Recife, Pernambuco, Brazil, by PCR and sequencing. RESULTS: The aac(6')-Ib-cr gene was detected in 16 resistant isolates, and the bla KPC gene was seen in 14. CONCLUSIONS: The presence of these genes in P. stuartii multi- and extensively drug-resistant isolates indicates that the resistance arsenal of this species is increasing, thus limiting the therapeutic options.

Clinical and drug resistance characteristics of Providencia stuartii infections in 76 patients.

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.

Emergence of Carbapenem-Resistant Providencia rettgeri and Providencia stuartii Producing IMP-Type Metallo-ß-Lactamase in Japan.

Four Providencia rettgeri isolates and one Providencia stuartii isolate were obtained from urine samples of five patients in 2018 in Japan. All of the isolates were resistant to imipenem and meropenem, and three were highly resistant to both carbapenems, with MICs of 512 µg/ml. The three highly carbapenem-resistant isolates harbored blaIMP-70, encoding a variant of IMP-1 metallo-ß-lactamase with two amino acid substitutions (Val67Phe and Phe87Val), and the other two harbored blaIMP-1 and blaIMP-11, respectively. Whole-genome sequencing revealed that an isolate harbored two copies of blaIMP-1 on the chromosome and that the other four harbored a copy of blaIMP-11 or blaIMP-70 in a plasmid. Expression of blaIMP-70 conferred carbapenem resistance in Escherichia coli Recombinant IMP-70 and an IMP-1 variant with Val67Phe but without Phe87Val had significant higher hydrolytic activities against meropenem than recombinant IMP-1, indicating that an amino acid substitution of Val67Phe affects increased activities against meropenem in IMP-70. These results suggest that Providencia spp. become more highly resistant to carbapenems by acquisition of two copies of blaIMP-1 or by mutation of blaIMP genes with amino acid substitutions, such as blaIMP-70.

Anthocyanins in Blueberries Grown in Hot Climate Exert Strong Antioxidant Activity and May Be Effective against Urinary Tract Bacteria.

Anthocyanins are extensively studied for their health-related properties, including antibacterial activity against urinary tract infections (UTI). Among common fruits, blueberries, with their remarkable antioxidant capacity, are one of the richest sources. Anthocyanin-rich extracts were obtained from four varieties: Snowchaser, Star, Stella Blue and Cristina Blue, grown in the hot climate of Southern Spain. Their total anthocyanins contents (TAC) were determined spectrophotometrically, and the anthocyanin profile by ultra high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS). Their antioxidant activity was assessed by oxygen radical absorbance capacity (ORAC) assay, while antibacterial activity against strains isolated from UTI patients was assessed in vitro, helping to select the varieties with the highest bioactive potential. Star showed the highest TAC and antioxidant activity (1663 ± 159 mg of cyanidin-3-O-glucoside (cy-3-O-glu) equivalents/100 g fresh weight (FW), 6345 ± 601 µmol Trolox equivalents (TE)/100 g FW, respectively), followed by Cristina Blue, Stella Blue and Snowchaser. As far as we know, this is the first time that cyanidin-3-rutinoside has been identified in blueberries. The extracts inhibited all the tested strains, MICs ranging from 0.4 mg/mL (for Stella Blue extract against UTI P. aeruginosa) to 9.5 mg/mL (for all extracts against UTI K. pneumoniae ssp. pneumoniae). This is the first study that assessed in vitro the antibacterial activity of blueberries against Klebsiella pneumoniae, Providencia stuartii and Micrococcus spp. strains isolated from UTI.

Transposon Insertion Site Sequencing of Providencia stuartii: Essential Genes, Fitness Factors for Catheter-Associated Urinary Tract Infection, and the Impact of Polymicrobial Infection on Fitness Requirements.

Providencia stuartii is a common cause of polymicrobial catheter-associated urinary tract infection (CAUTI), and yet literature describing the molecular mechanisms of its pathogenesis is limited. To identify factors important for colonization during single-species infection and during polymicrobial infection with a common cocolonizer, Proteus mirabilis, we created a saturating library of ∼50,000 transposon mutants and conducted transposon insertion site sequencing (Tn-Seq) in a murine model of CAUTI. P. stuartii strain BE2467 carries 4,398 genes, 521 of which were identified as essential for growth in laboratory medium and therefore could not be assessed for contribution to infection. Using an input/output fold change cutoff value of 20 and P values of <0.05, 340 genes were identified as important for establishing single-species infection only and 63 genes as uniquely important for polymicrobial infection with P. mirabilis, and 168 genes contributed to both single-species and coinfection. Seven mutants were constructed for experimental validation of the primary screen that corresponded to flagella (fliC mutant), twin arginine translocation (tatC), an ATP-dependent protease (clpP), d-alanine-d-alanine ligase (ddlA), type 3 secretion (yscI and sopB), and type VI secretion (impJ). Infection-specific phenotypes validated 6/7 (86%) mutants during direct cochallenge with wild-type P. stuartii and 3/5 (60%) mutants during coinfection with P. mirabilis, for a combined validation rate of 9/12 (75%). Tn-Seq therefore successfully identified genes that contribute to fitness of P. stuartii within the urinary tract, determined the impact of coinfection on fitness requirements, and added to the identification of a collection of genes that may contribute to fitness of multiple urinary tract pathogens.IMPORTANCEProvidencia stuartii is a common cause of polymicrobial catheter-associated urinary tract infections (CAUTIs), particularly during long-term catheterization. However, little is known regarding the pathogenesis of this organism. Using transposon insertion site sequencing (Tn-Seq), we performed a global assessment of P. stuartii fitness factors for CAUTI while simultaneously determining how coinfection with another pathogen alters fitness requirements. This approach provides four important contributions to the field: (i) the first global estimation of P. stuartii genes essential for growth in laboratory medium, (ii) identification of novel fitness factors for P. stuartii colonization of the catheterized urinary tract, (iii) identification of core fitness factors for both single-species and polymicrobial CAUTI, and (iv) assessment of conservation of fitness factors between common uropathogens. Genomewide assessment of the fitness requirements for common uropathogens during single-species and polymicrobial CAUTI thus elucidates complex interactions that contribute to disease severity and will uncover conserved targets for therapeutic intervention.

Application of Arjuna (Terminalia arjuna) seed biochar in hybrid treatment system for the bioremediation of Congo red dye.

In the present study, a hybrid treatment system (biological and ozonation) was developed and used in the decolorization of Congo red (CR) dye. The biological treatment was performed in packed bed bioreactor (PBBR) containing Arjuna (Terminalia Arjuna) seeds biochar immobilized with Providencia stuartii, whereas ozonation was carried out in an ozone reactor. The process variables such as temperature, process time, and inoculum size were optimized and found to be 30 °C, 2 48 h, and 3 × 105 CFU/mL, respectively with 92.0 ± 5.0% of dye decolorization. Furthermore, biologically treated effluent was subject to ozone treatment for the decolorization of the remaining CR dye. The hybrid approach reveals almost complete decolorization of Congo red (CR) dye. The kinetic study of microbial growth was examined by Monod model. In addition, the cost analysis estimation for the removal of CR dye was done, and removal per liter was found to be economic.

Removal of dimethachlon from soils using immobilized cells and enzymes of a novel potential degrader Providencia stuartii JD.

The first potential degrader capable of detoxifying dimethachlon (NDPS) was isolated and identified as Providencia stuartii JD, whose free cells and freely crude enzymes degraded more than 80% and 90% of 50 mg L-1 NDPS in liquid culture within 7 d and 2 h, respectively. Strain JD metabolized NDPS through the typical pathway, in which NDPS was firstly transformed into succinic acid and 3, 5-dichloroanilin, and the latter was then converted to phenol, which was subsequently degraded to muconic acid further subjected to the mineralization. The immobilization obviously improved the stability and adaptability of cells and enzymes. In laboratory non-sterile soils treated by free or immobilized cells and enzymes, 50 mg kg-1 NDPS decreased to 15.66 and 13.32 mg kg-1, or 8.32 and 2.18 mg kg-1 within 7 d, respectively. In field, immobilized cells and enzymes exhibited significantly higher efficiencies in removing 20.250 kg a.i. ha-1 NDPS wettable powder from soils after 9 d (96.02% and 98.56%) than free cells and enzymes (79.35% and 66.45%). This study highlights that strain JD promises the great potential to remove hazardous NDPS residues and its immobilized cells and enzymes possess the more promising advantages in the bioremediation of NDPS-contaminated soils in situ.

Dissemination of NDM-1 carbapenemase-producer Providencia stuartii strains in Romanian hospitals: a multicentre study.

Several Romanian hospitals have noted increasing isolation of Providencia stuartii strains in recent years, with an alarming rate of carbapenem resistance. In order to provide molecular epidemiological data regarding their dissemination, 77 P. stuartii strains collected from five hospitals located in different regions of Romania were analysed. All strains harboured IncA/C plasmid, and 67 carried the blaNDM-1 gene. Six clonal clusters were differentiated by pulsed-field gel electrophoresis. The predominant subtype was found in all five hospitals. Our study highlights the need for efficient infection-control measures, the optimization of antibiotic use and the targeted surveillance for carbapenemase-producing P. stuartii.

d-Serine Degradation by Proteus mirabilis Contributes to Fitness during Single-Species and Polymicrobial Catheter-Associated Urinary Tract Infection.

Proteus mirabilis is a common cause of catheter-associated urinary tract infection (CAUTI) and secondary bacteremia, which are frequently polymicrobial. We previously utilized transposon insertion-site sequencing (Tn-Seq) to identify novel fitness factors for colonization of the catheterized urinary tract during single-species and polymicrobial infection, revealing numerous metabolic pathways that may contribute to P. mirabilis fitness regardless of the presence of other cocolonizing organisms. One such "core" fitness factor was d-serine utilization. In this study, we generated isogenic mutants in d-serine dehydratase (dsdA), d-serine permease (dsdX), and the divergently transcribed activator of the operon (dsdC) to characterize d-serine utilization in P. mirabilis and explore the contribution of this pathway to fitness during single-species and polymicrobial infection. P. mirabilis was capable of utilizing either d- or l-serine as a sole carbon or nitrogen source, and dsdA, dsdX, and dsdC were each specifically required for d-serine degradation. This capability was highly conserved among P. mirabilis isolates, although not universal among uropathogens: Escherichia coli and Morganella morganii utilized d-serine, while Providencia stuartii and Enterococcus faecalis did not. d-Serine utilization did not contribute to P. mirabilis growth in urine ex vivo during a 6-h time course but significantly contributed to fitness during single-species and polymicrobial CAUTI during a 96-h time course, regardless of d-serine utilization by the coinfecting isolate. d-Serine utilization also contributed to secondary bacteremia during CAUTI as well as survival in a direct bacteremia model. Thus, we propose d-serine utilization as a core fitness factor in P. mirabilis and a possible target for disruption of infection.IMPORTANCE Urinary tract infections are among the most common health care-associated infections worldwide, the majority of which involve a urinary catheter (CAUTI). Our recent investigation of CAUTIs in nursing home residents identified Proteus mirabilis, Enterococcus species, and Escherichia coli as the three most common organisms. These infections are also often polymicrobial, and we identified Morganella morganii, Enterococcus species, and Providencia stuartii as being more prevalent during polymicrobial CAUTI than single-species infection. Our research therefore focuses on identifying "core" fitness factors that are highly conserved in P. mirabilis and that contribute to infection regardless of the presence of these other organisms. In this study, we determined that the ability to degrade d-serine, the most abundant d-amino acid in urine and serum, strongly contributes to P. mirabilis fitness within the urinary tract, even when competing for nutrients with another organism. d-Serine uptake and degradation therefore represent potential targets for disruption of P. mirabilis infections.