Five-Year Analysis of afa Gene Prevalence in Uropathogenic Escherichia coli Isolates: A Global Perspective

Abstract

The human body hosts a diverse array of microorganisms, including commensal organisms and those that cause various diseases. Urinary tract infections (UTIs) are among the most prevalent infections worldwide, second only to respiratory tract infections. Uropathogenic Escherichia coli (UPEC) is the primary causative agent of UTIs because of its numerous virulence factors that contribute to infection and penetration of the host's mucosal barrier [1]. Among these virulence factors, the ability to adhere to host cells is crucial.

UPEC possesses a genome containing various genes carried on operons, including those responsible for adhesion and biofilm formation, such as pap (prevalent in pyelonephritis-associated strains), fim (found in nearly all UPEC isolates), sfa, and afa [2]. The afa gene is one such adhesion-related genes in UPEC, mediating afimbrial adhesion. It functions by producing adhesive polymeric substances on the bacterial cell surface and certain proteins that enhance bacterial binding to host cells [3]. The afa operon consists of afaA through afaF. The A and F segments are involved in encoding transcription systems, B segments correspond to proteins in the cytoplasmic space, C segments anchor the protein, D is responsible for invasion, and E is responsible for cell adhesion [4].

Adhesion to urinary tract epithelial cells provides a favorable environment for bacterial growth, leading to infection development and associated symptoms. The presence of the afa gene in E. coli is associated with pyelonephritis. Indeed, it concentrates in the most virulent isolates [5]. In this letter, we sought to provide an overview of the prevalence of the afa gene in UPEC causing UTIs worldwide as no previous study reported such data.

In the middle east region, Syria in particular, an afa gene distribution rate of 18.3% was obtained. It turned out that most isolates were from pregnant women and exhibited resistance to multiple antibiotics. Similarly, an Iraqi study in 2024 reported a slightly higher prevalence of afa-expressing isolates (14.28%), demonstrating its contribution to biofilm formation and increased infection severity, particularly in pyelonephritis [6]. Additional studies from Iraq [7] and Iran [8] reported afa gene prevalence rates of 12.7%, 15.6%, and 11%, respectively. The Iranian study noted a correlation between the gene's presence and antibiotic resistance, particularly in regions with indiscriminate antibiotic use, and a higher prevalence in females, especially pregnant women.

Highest prevalence rates were found in India and Southeast Asia where hygiene and medical care are insufficient. An Indian study [9] identified a prevalence rate as high as 23.1%. Studies from Thailand [10] have also linked the afa gene to increased virulence and bladder infections in children and pregnant women, respectively.

In the United States, a decreasing trend in afa gene prevalence was recorded since 2015, emphasizing that variations among isolates depend on environmental factors, in addition to the increased awareness as well as the health policies to prevent the emergence of antibiotic-resistant strains and those that are devoid of such gene [11].

In South America, represented by Brazil, Daga et al. [12] obtained a low prevalence rate of 10.4% in comparison with other regions worldwide. This rate is significantly lower than other regions globally, but not lower than Europe.

European countries recorded the least prevalence rate of afa-expressing UPEC (represented by 7.7% in Russia and Ireland). This makes sense as these countries are characterized by a well-supported medical sector and hygiene practices in addition to having firm restrictions for antibiotics prescription from the health decision makers as well as increased awareness of antibiotic use and its impact on reducing the spread of resistant strains [5, 13]. Figure 1 displays the prevalence rate of UPEC expressing the afa gene globally in the recent 5 years.

Indeed, UPEC isolates expressing the afa gene are linked to biofilm formation and recurrent UTIs in pregnant women [14]. A study in 2022 confirmed the association between the afa gene and pyelonephritis [3]. Although the afa gene prevalence is low in most UPEC studies, some studies have reported higher rates than other geographical regions. All these studies suggest that UPEC is a concern because of its ability to acquire new genes, leading to resistance against multiple antibiotics and making treatment challenging [15].

This investigation emphasizes the need for continued research on virulence-associated genes in UPEC to understand their evolution and impact on public health. The variations in prevalence rates may be attributed to indiscriminate antibiotic use, leading to more virulent strains, or to varying environmental factors, such as malnutrition and conditions in developing countries. The gene is also more prevalent in children and pregnant women, with variations depending on the patient's condition. The afa gene prevalence in UPEC has shown notable variations, highlighting the influence of environmental, geographical, and indiscriminate antibiotic use. These findings underscore the urgent need for enhanced research in medical microbiology and the development of sustainable health policies to limit the spread of virulence factors in UPEC and their antibiotic resistance.

The authors declare no conflicts of interest.