Metabolic interplay between and facilitates polymicrobial biofilm formation and invasive disease.

Biofilms play an important role in the development and pathogenesis of catheter-associated urinary tract infection (CAUTI). and are common CAUTI pathogens that persistently co-colonize the catheterized urinary tract and form biofilms with increased biomass and antibiotic resistance. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution to CAUTI severity.

Function and contribution of two putative glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection.

is a common cause of healthcare-acquired bloodstream infections and catheter-associated urinary tract infections (CAUTIs) in both adults and children. Treatment of infection is frequently complicated by multi-drug resistance. Based on protein homology, encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB).

Function and contribution of two putative glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection.

is a common cause of healthcare acquired bloodstream infections and catheter associated urinary tract infections (CAUTI) in both adults and children. Treatment of infection is frequently complicated by multi-drug resistance. Based on protein homology, encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB).

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

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 CAUTI: a Hyb-type Group 1c H-uptake hydrogenase and a Hyf-type Group 4a H-producing hydrogenase. In this study, we disrupted one gene of each system ( and ) and also generated a double mutant to examine the contribution of flexible H metabolism to growth and fitness in vitro and during experimental CAUTI.

Metabolic interplay between and facilitates polymicrobial biofilm formation and invasive disease.

Polymicrobial biofilms play an important role in the development and pathogenesis of CAUTI. and are common CAUTI pathogens that persistently co-colonize the catheterized urinary tract and form biofilms with increased biomass and antibiotic resistance. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution to CAUTI severity.

Preferential catabolism of l- vs d-serine by Proteus mirabilis contributes to pathogenesis and catheter-associated urinary tract infection.

Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter-associated urinary tract infection (CAUTI), particularly those for d- and l-serine.

Prospective assessment of catheter-associated bacteriuria clinical presentation, epidemiology, and colonization dynamics in nursing home residents.

BACKGROUNDCatheterization facilitates continuous bacteriuria, for which the clinical significance remains unclear. This study aimed to determine the clinical presentation, epidemiology, and dynamics of bacteriuria in a cohort of long-term catheterized nursing home residents.METHODSProspective urine culture, urinalysis, chart review, and assessment of signs and symptoms of infection were performed weekly for 19 study participants over 7 months.

Catalase Activity is Critical for Proteus mirabilis Biofilm Development, Extracellular Polymeric Substance Composition, and Dissemination during Catheter-Associated Urinary Tract Infection.

Proteus mirabilis is a leading uropathogen of catheter-associated urinary tract infections (CAUTIs), which are among the most common health care-associated infections worldwide. A key factor that contributes to P. mirabilis pathogenesis and persistence during CAUTI is the formation of catheter biofilms, which provide increased resistance to antibiotic treatment and host defense mechanisms.

Polymicrobial Interactions Facilitate Biofilm Formation, Antibiotic Recalcitrance, and Persistent Colonization of the Catheterized Urinary Tract.

Indwelling urinary catheters are common in health care settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, we identified and as the most prevalent and persistent co-colonizers.

Ynt is the primary nickel import system used by Proteus mirabilis and specifically contributes to fitness by supplying nickel for urease activity.

Proteus mirabilis is a Gram-negative uropathogen and frequent cause of catheter-associated urinary tract infection (CAUTI). One important virulence factor is its urease enzyme, which requires nickel to be catalytically active. It is, therefore, hypothesized that nickel import is critical for P.

A Rare Opportunist, , Decreases Severity of Polymicrobial Catheter-Associated Urinary Tract Infection.

Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood. is one of the most common causes of monomicrobial and polymicrobial CAUTI and frequently cocolonizes with , , , and infections are particularly challenging due to its potent urease enzyme, which facilitates formation of struvite crystals, catheter encrustation, blockage, and formation of urinary stones.

Twin arginine translocation, ammonia incorporation, and polyamine biosynthesis are crucial for Proteus mirabilis fitness during bloodstream infection.

The Gram-negative bacterium Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTI), which can progress to secondary bacteremia. While numerous studies have investigated experimental infection with P. mirabilis in the urinary tract, little is known about pathogenesis in the bloodstream.

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

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 fitness regardless of the presence of other cocolonizing organisms. One such "core" fitness factor was d-serine utilization.

Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin.

Background: Persistence of bacterial pathogens in the airways has profound consequences on the course and pathogenesis of chronic obstructive pulmonary disease (COPD). Patients with COPD continuously acquire and clear strains of Moraxella catarrhalis, a major pathogen in COPD. Some strains are cleared quickly and some persist for months to years.

A Cation-Binding Surface Protein as a Vaccine Antigen To Prevent Moraxella catarrhalis Otitis Media and Infections in Chronic Obstructive Pulmonary Disease.

is an exclusively human respiratory tract pathogen that is a common cause of otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent these infections would have a major impact on reducing the substantial global morbidity and mortality in these populations. Through a genome mining approach, we identified AfeA, an ∼32-kDa substrate binding protein of an ABC transport system, as an excellent candidate vaccine antigen.

Antimicrobial activity of antisense peptide-peptide nucleic acid conjugates against non-typeable Haemophilus influenzae in planktonic and biofilm forms.

Background: Antisense peptide nucleic acids (PNAs) are synthetic polymers that mimic DNA/RNA and inhibit bacterial gene expression in a sequence-specific manner.

Methods: To assess activity against non-typeable Haemophilus influenzae (NTHi), we designed six PNA-peptides that target acpP, encoding an acyl carrier protein. MICs and minimum biofilm eradication concentrations (MBECs) were determined.

ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence.

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities.

Sulfate-binding protein, CysP, is a candidate vaccine antigen of Moraxella catarrhalis.

Moraxella catarrhalis causes otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). A vaccine to prevent M. catarrhalis infections would have an enormous impact globally in preventing morbidity caused by M.

Role of the oligopeptide permease ABC Transporter of Moraxella catarrhalis in nutrient acquisition and persistence in the respiratory tract.

Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival.

Role of the zinc uptake ABC transporter of Moraxella catarrhalis in persistence in the respiratory tract.

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested.

Expression of urease by Haemophilus influenzae during human respiratory tract infection and role in survival in an acid environment.

Background: Nontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Prior studies have shown that H. influenzae expresses abundant urease during growth in the middle ear of the chinchilla and in pooled human sputum, suggesting that expression of urease is important for colonization and infection in the hostile environments of the middle ear and in the airways in adults.

Proteomic expression profiling of Haemophilus influenzae grown in pooled human sputum from adults with chronic obstructive pulmonary disease reveal antioxidant and stress responses.

Background: Nontypeable Haemophilus influenzae colonizes and infects the airways of adults with chronic obstructive pulmonary disease, the fourth most common cause of death worldwide.Thus, H. influenzae, an exclusively human pathogen, has adapted to survive in the hostile environment of the human airways.

Pseudomonas aeruginosa population biology in chronic obstructive pulmonary disease.

Background: The role played by airway infections with Pseudomonas aeruginosa in the course and pathogenesis of chronic obstructive pulmonary disease (COPD) has not yet been resolved. We report on the molecular epidemiology and population biology of P. aeruginosa in COPD.

Characterization of proteins Msp22 and Msp75 as vaccine antigens of Moraxella catarrhalis.

Moraxella catarrhalis is a respiratory tract pathogen causing otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. This study examined two newly identified proteins as potential vaccine antigens. Antisera raised to recombinant purified proteins Msp22 and Msp75 recognized corresponding native proteins in multiple strains of M.