Loss of fliCD Gene in Multidrug-Resistant UPEC: Clinical Implications and Treatment
The absence of the fliCD virulence gene in multidrug-resistant uropathogenic E. coli (UPEC) indicates reduced capacity for ascending kidney infection, suggesting these strains may cause primarily lower urinary tract infections that are less likely to progress to pyelonephritis, though their multidrug resistance still necessitates culture-guided antibiotic therapy.
Virulence Implications of fliCD Gene Loss
The fliCD gene encodes flagellar components essential for bacterial motility in UPEC. Loss of this gene has specific consequences for infection patterns:
Reduced kidney colonization capacity: Flagella-deficient UPEC strains demonstrate significantly impaired ability to ascend from the bladder into the kidneys in experimental models, with fliC mutants showing compromised kidney invasion at 12 hours post-inoculation compared to wild-type strains 1.
Maintained bladder colonization: Despite loss of flagellar function, these strains can still colonize the urinary tract during independent challenge, indicating that flagella are not absolutely required for initial bladder infection but significantly enhance pathogenic fitness 2.
Trade-off with antibiotic resistance: The observation that multidrug-resistant UPEC more frequently lack fliCD suggests a potential fitness trade-off where bacteria invest metabolic resources in resistance mechanisms rather than motility factors 3.
Clinical Presentation Expectations
Patients infected with fliCD-negative, multidrug-resistant UPEC will likely present with:
Lower urinary tract symptoms predominating: Dysuria, frequency, urgency, and suprapubic discomfort without systemic features 4.
Lower risk of ascending pyelonephritis: The absence of flagella-mediated motility reduces the likelihood of progression to upper tract infection with fever, flank pain, and systemic toxicity 1.
Potential for persistent bladder colonization: These strains may establish quiescent intracellular reservoirs within bladder epithelium through adhesins and invasins, independent of flagellar function 3.
Treatment Approach
Initial Management
Obtain urine culture with antimicrobial susceptibility testing before initiating empiric therapy, as multidrug resistance patterns require targeted antibiotic selection 3.
Empiric therapy considerations: While awaiting culture results, select agents based on local antibiogram data and patient-specific risk factors for resistance 3.
Avoid fluoroquinolones and trimethoprim-sulfamethoxazole empirically: These agents face increasing resistance rates in multidrug-resistant UPEC isolates 3.
Definitive Therapy
Culture-directed antibiotic selection: Adjust therapy based on susceptibility results, prioritizing agents with demonstrated in vitro activity 3.
Consider nitrofurantoin or fosfomycin: These agents may retain activity against multidrug-resistant strains for uncomplicated lower UTI, though susceptibility must be confirmed 3.
Reserve carbapenems and other broad-spectrum agents: Use only when susceptibility data support their necessity to minimize further resistance development 3.
Duration and Monitoring
Standard duration for uncomplicated cystitis: 3-7 days depending on agent selected, as the reduced virulence profile (lack of flagella) suggests lower risk of complicated infection 2, 1.
Clinical reassessment at 48-72 hours: Ensure symptom improvement; lack of response warrants repeat culture and consideration of alternative diagnoses 3.
Important Caveats
Multidrug resistance remains the primary concern: Despite reduced virulence from fliCD loss, treatment failure due to antibiotic resistance poses greater morbidity risk than the virulence factor profile 3.
Other virulence factors remain functional: These strains retain adhesins (type 1 pili), iron-acquisition systems, toxins, and invasion capabilities that enable bladder colonization and persistence 3, 4, 5.
Host factors modify risk: Immunocompromised patients, those with urinary tract abnormalities, or pregnant women require more aggressive management regardless of bacterial virulence factor profile 4.
Biofilm formation capacity persists: Intracellular bacterial communities can form independent of flagellar function, contributing to recurrent infections 3.