Adhesion and biofilm genes play a major role in the pathogenicity of S. aureus and its ability to cause food poisoning. Adhesion refers to the potential of S. aureus to attach to surfaces, such as host tissues or abiotic surfaces like medical devices and food contact surfaces. Drawing from this information, it can be concluded that adhesion is crucial for the first establishment of infections and subsequently tissues invasion [14, 15]. Derived from the aforementioned content, understanding the mechanisms of adhesion and biofilm formation including its involved genes in S. aureus is of utmost importance for developing strategies to prevent and treat S. aureus infections and foodborne diseases [4]. Given this, currently, numerous studies are examining the prevalence of adhesion and biofilm genes, their expression levels under diverse conditions, and their precise involvement in pathogenesis [8].
The current study focused on examining the occurrence rate of 15 adhesion and biofilm genes, which are highly more studied, and explored their interconnections among S. aureus isolates. Based on the findings regarding absolute and relative prevalence, it was observed that genes such as clf, particularly clfB, as well as eno and icaD, exhibited a high prevalence among S. aureus isolates. There have been several studies reporting a 100% presence of clfA [16–20] and clfB [17, 19, 20] genes among the examined S. aureus isolates. These studies indicate that these genes are highly conserved and prevalent in the S. aureus population, at least within the specific cohorts or settings investigated.
In contrast, several studies have reported the prevalence of clfA and clfB genes in S. aureus isolates to be less than 50% [21–24]. These findings suggest that the presence of clfA and clfB genes can vary among different populations of S. aureus isolates. However, it is important to express that these findings may not necessarily be representative of the entire S. aureus population, as the prevalence of genes can vary across different strains, geographic locations of samples, and patient or sample populations [25]. Therefore, it is crucial to consider the context and limitations of individual studies when interpreting the prevalence of adhesion and biofilm genes in S. aureus isolates.
Based on our findings, it has been determined that the icaADBC operon genes (particularly icaA: p- estimate = 61.7; and icaD: p-estimale = 77) exhibit a high prevalence rate among S. aureus isolates. It appears that, while some studies have reported presence rates below 50% for the icaADBC operon genes [16, 26], it is noteworthy that studies reporting presence rates above 50% are more prevalent [27, 28]. Furthermore several previous studies have even reported 100% presence rates for these genes [23, 24]. It well known that the product of icaADBC plays important roles in the synthesis of PIA, also known as poly-N-acetylglucosamine (PNAG) which is a key component of the biofilm matrix, allows S. aureus cells to adhere to surfaces and form cohesive structure of biofilm [29]. Indeed, the high prevalence rate of the icaADBC operon genes in S. aureus isolates is noteworthy due to their major impacts on bacterial biofilm formation and pathogenicity [29]; therefore these data could be applicable for novel therapeutic strategies targeting S. aureus bacteria specially for biofilm-related infections.
Another prevalent studied gene was sasG (p-estimate = 74.8) which encodes S. aureus surface protein G (SasG), a large surface protein (120–240 kD) that plays a role in adhesion and biofilm formation. These proteins mediate the binding of bacteria to host tissues and extracellular matrix components such as fibrinogen, fibronectin, and elastin. It facilitates the initial attachment of the bacteria to host tissues and surfaces, contributing to the establishment of infections. In addition to its role in adhesion, SasG has been implicated in biofilm formation [5, 8].
On the opposite side the prevalence of bap and bbp, being present in only 6.7% and 18.7% of the isolates, respectively, suggests that these genes are less prevalent among the studied S. aureus isolates. However, it is important to note that the low frequency of these genes does not necessarily imply that they have low importance in adhesion and biofilm formation. The presence or absence of specific genes alone cannot determine their significance or impact on adhesion and biofilm formation [30]. It is possible that other genes or mechanisms may compensate for the absence or low prevalence of bap and bbp in these isolates. Moreover, the importance of adhesion and biofilm formation in S. aureus can be attributed to a complex interplay of multiple factors, including the presence of various adhesion genes, regulatory mechanisms, host factors, and environmental conditions. Therefore, the role and importance of a specific gene in these processes cannot be solely determined based on its frequency of occurrence [11, 31]. The main debatable result arising from the current study is the limited number of investigations carried out on sasG, bbp, bap and eno with 5, 6, 7 and 9 studies, respectively. This low data can pose challenges in drawing definitive conclusions and generalizing the results for the exact presence rates of these genes. Certainly increased research efforts in exploring these genes would contribute to a deeper understanding of their importance in S. aureus pathogenicity and facilitate the development of targeted interventions or therapies in the future.
In the next step of study, according to the results obtained from the network meta-analysis regarding the prevalence of co-studied between two genes in the included studies (Fig. 5), it can be expressed that previous researchers mainly focused on studying the icaADBC operon to explore adhesion mechanism and biofilms formation of S. aureus.
Among the genes of the icaADBC operon, the highest co-studied genes were icaD-icaA. Considering these findings, it becomes apparent that the icaA encodes the N-acetylglucosamyl transferase enzyme, which is responsible for PIA synthesis. Although this enzyme shows limited activity, the co-expression of the icaD enhances its activity. This suggests that the icaD product somehow facilitates or enhances the function of the enzyme [29]. Additionally, from MSCRAMMs, fnbA-fnbB has received special attention in previous studies due to their unique roles. These genes encode fibronectin-binding proteins which play a crucial role in adhesion, invasion, immune evasion, and biofilm formation. They facilitate the attachment of S. aureus to fibronectin, allowing the bacteria to colonize host tissues and establish infections such as endocarditis [32] and mastitis [33]. Besides, fnbA and fnbB contribute to immune evasion mechanisms and are involved in the formation of antibiotic-resistant biofilms [4]. As a result, understanding the prevalence rate and specific functions of FnbA and FnbB is valuable for developing effective strategies to combat S. aureus infections.
Given the very limited number of studies exploring the connection between the origin of the isolate and the prevalence of adhesion genes, the current investigation focused on addressing this issue. Consequently, our subgroup analysis revealed that, apart from the icaC and icaB, which were found to be lower in animal isolates, there were no significant variations in the prevalence of the other studied genes among the isolates (Fig. 6). The significant disparity observed (related to icaC and icaB) seems to be attributed to the scarcity of analyzed data, as only these genes were present in 4 animal studies. Consequently, the present study suggests the requirement for further investigations to establish the precise correlation between the adhesion and biofilm genes with the origin of the isolate.
The significant outcome of the present study is the limited accessibility of data for analyzing the prevalence of sasG, bbp, bap, eno, and fib especially in relation to animal isolates. As a result, considering the pivotal role of these mentioned genes in S. aureus adhesion and biofilm formation [4, 5, 34], it is crucial to conduct further studies to investigate the exact prevalence rate these genes in future studies.