الفهرس 
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Abstract
Proteus mirabilis is a widely disseminated bacterium in the environment and is also
responsible for most Proteus infections especially in human urinary tract. P. mirabilis can
cause several infections mainly urinary tract infections, wound infections, bacteremia and
others. P.mirabilis pathogenicity is mediated by various virulence factors including adhesins
which contribute to biofilm formation, flagella that control motility and swarming, toxins for
invasion and quorum-sensing that play a critical role in the biofilm formation too. Moreover,
it has the ability to produce several enzymes such as urease that breakdown the urea into
ammonia and carbon dioxide which increases the pH of urine causing stone formation.
Emergence and spread of MDR P. mirabilis isolates within clinical settings can occur
via bacterial cross-transmission or contamination arising from an environmental source.
Resistance determinants in these bacteria can be acquired through horizontal gene transfer,
which represents a serious hazard to the management of infectious diseases and restricts
therapeutic choices.
Studying different classes of integrons harboring different gene cassettes at genotypic
level and its intimate connection to accumulation of phenotypic antimicrobial resistance, is a
corner stone for setting up a strategy to control MDR and XDR bacterial isolates that
represent a huge obstacle for management of different infections. Also the study of integrons
and its intricate connection between cell physiology components, feature these platforms as
compelling tools for genome innovation and bacterial adaptation.
The aim of the study was to investigate phenotypic and molecular characterization of
antimicrobial resistance in P. mirabilis from different clinical specimens. This study was
carried out during a period of 18 months. During this period a total of 100 clinical isolates of
P. mirabilis, were collected from different clinical specimens from different microbiological
labs of Alexandria governorate.
Identification of P. mirabilis was achieved by conventional methods, including
morphology, culture characteristics and traditional biochemical tests. Susceptibility of P.
mirabilis isolates to different antibiotics was examined by Kirby-Bauer disk diffusion method
according to CLSI recommendations 2021.
The majority of P. mirabilis isolates were isolated from urinary tract infections (75%),
followed by wound infection (21%). Variable degrees of antimicrobial resistance of P.
mirabilis isolates to the tested antibiotics were detected with approximately 34% of the
isolates being multidrug-resistant (MDR) and 9% were extensively drug-resistant (XDR).
Molecular characterization of different integrons revealed that 93% of the isolates were
positive for integrons with predominance of IntI 1&2. Additionally, IVRs were successfully
detected in most of IntI 1 & IntI 2 positive P. mirabilis isolates. Different resistance gene
cassette arrays in the clinical isolates of P. mirabilis were detected with prevalence of gene
cassette associated drug class resistance for aminoglycosides and sulphonamides.
Summary, Conclusion & Recommendations
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Significant prevalence of MDR and XDR phenotypic antibiotic patterns of resistance in
isolates that carry IntI 1 & IntI 2 together was detected. Compared to Non-MDR, MDR
strains significantly carried two classes of integrons together, while XDR significantly carried
class 1, 2 & 3 integrons simultaneously. Additionally, compared to integrase-negative strains,
strains that carried integrons had a higher rate of resistance to different antibiotics except for
IntI 3. Moreover, there was a highly significant association between strains carrying IntI
1gene and Sul-1&QacEΔ1 gene detection, and also between Sul-1&QacEΔ1 gene detection
and SXT phenotypic antibiotic resistance.
6.2. Conclusions:
- Proteus mirabilis is responsible for most of Proteus infections, and it is common in
infections of the urinary tract.
- MDR and XDR P. mirabilis isolates are prevalent in clinical samples (43%)
- Integrons are common among MDR and XDR isolates of P. mirabilis. For being able to
integrate, express, and disseminate gene cassettes and carrying resistance determinants,
it could be used as a marker for the identification of patterns of antimicrobial resistance
to different antibiotics within P. mirabilis isolates.
- The findings scored the important role of Class 1 integron as a dominant player in the
spreading of antibiotic resistance genes through carrying different resistance gene
cassettes for antimicrobial resistance especially encoding for aminoglycoside and SXT
resistance.
- Although low distribution and relatively conserved molecular characteristics are the
main traits of class 2 integrons, functional IntI 2 have low distribution and relatively
conserved molecular characteristics, they may still form clinical dissemination and drug
resistance expression due to high prevalence of gene cassettes encoding for betalactamases.
- An alarming trend of increased resistance to SXT among class 1 integrase positive
strains of P. mirabilis was noted.
6.3. Recommendations:
The rising of MDR and XDR isolates is a problem that complicates treatment of
infection, therefore high restrictions must be applied for antibiotic prescription and
susceptibility testing must be done before antibiotic dispensing to limit the dissemination and
persistence of MDR/XDR P. mirabilis isolates in the population.
Urgent work is required to employ effective means to avoid dissemination of MDR
isolates beause of the possibility of widespread outbreaks of such bacteria, therefore
molecular surveillance and sequencing of the integrons are recommended to be applied.
Resistance phenotypes are quikly disseminated by integrons which makes it important
to consider what other integron-mediated characterestics, such as aggravated pathogenicity
and virulence might affect human health in the future.
Understanding the de novo creation of gene cassettes and defining the functional
diversity of them will enable better presumptive control on bacterial growth, while also
promoting development of technologies that could employ integron activity.
If integrons and cassette formation could be controlled, we could use integrons as a
platform to establish novel biochemical pathways to control antimicrobial resistance.
Therefore, studying the prevalence of integrons and associated various gene cassettes is
advantageous for the treatment and correct use of antibiotics.