## 1 Introduction  
The emergence of new antimicrobial-resistant pathogens represents a global challenge due to the transfer of bacteria between the environment, humans and animals [1]. During this transfer, pathogens acquire new antibiotic-resistant genetic elements, thus hindering our ability to treat bacterial infections [1]. In 2014, it was estimated that by 2050 the death rate would be 10 million due to resistant infections [2]. Moreover, more than 60% of nosocomial infections are caused by biofilm-producing microbes, which is considered a major clinical challenge due to their extracellular polymeric matrix that is difficult to penetrate [3]. Microbial biofilm can tolerate up to 100-1000 times more antibiotics than their planktonic-free cell counterparts [4]. Therefore, the WHO reported in 2020 that antibiotic resistance is a global challenge and possesses a high priority for promoting research and developing novel antimicrobials against multidrug-resistant pathogens [5]. Unfortunately, antibiotic resistance is still in progress, and there were an estimated 4.95 million deaths associated with drug-resistant infections in 2019, of which 1.27 million deaths were directly attributed to drug resistance [6]. One of the leading pathogens contributing to the burden of antimicrobial resistance in 2019 and the priority target for the development of alternative therapeeutics and new antimicrobial agents is the opportunistic pathogen _Pseudomonas aeruginosa_[6; 7]. _P. aeruginosa_ is a ubiquitous Gram-negative bacterium considered a leading pathogen in immunocompromised patients [8]. This bacterium is dominant in patients with cystic fibrosis because of its ability to promote the establishment of a microbial community in the airways, leading to prolonged chronic infections and rapid lung damage and mortality [9]. Furthermore, it is an important causative agent of chronic wound infections [10]. Biofilm formation, pigment secretion of pyocyanin and protease production make _P. aeruginosa_ a major food spoilage bacterium, and its presence in water can contaminate food and can transfer from infected asymptomatic animals to the excreted milk and meat [11; 12; 13]. The physiological and genetic determinants of _P. aeruginosa_ make it resilient to environmental changes and cause persistent infections that are difficult to treat [8]. The low susceptibility of most _P. aeruginosa_ strains to many antibiotics arises from their intrinsic core genome, which encodes virulence and antibiotic-resistant determinants [14]. Moreover, their ability to produce a biofilm leads to more antibiotic tolerance and antimicrobial failure. A biofilm is a heterogeneous and dynamic microenvironment; it is a set of different phenotypes, including susceptible actively growing cells, resistant cells and dormant persister cells [15; 16]. The diversity of the biofilm population arises as a consequence of the nutrient and oxygen gradient in the biofilm while growing, which changes the phenotypic characteristics and gene expressions of the embedded cells [15; 16]. Therefore, the development of new antimicrobial agents against _P. aeruginosa_ is urgently needed [8; 15]. One of the promising antimicrobial approaches that may overcome the development of resistance in the near future is photodynamic inactivation [17; 18]. The principle of photodynamic inactivation (PDI), antimicrobial photodynamic therapy (PDT), or antimicrobial photodynamic inactivation (aPDI) is based on the excitation of a non-toxic photosensitizer (PS) compound with a light source with a spectrum appropriate for the excitation of the PS (from the visible to infrared spectrum) in the presence of molecular oxygen, resulting in the generation of reactive oxygen species targeting different cellular structures and metabolic pathways [17; 19]. aPDI may lead to bacterial eradication or irreversible changes in the bacterial cells in such a way that it is difficult for the bacterial cell to recover or form resistance [18]. Therefore, aPDI has a low risk of causing resistance [18].