Pseudomonas aeruginosa biofilm is a community of bacteria that adhere to live or non-living surfaces and are encapsulated by an extracellular polymeric substance. Unlike individual planktonic cells, biofilms possess a notable inherent resistance to sanitizers and antibiotics. Overcoming this resistance is a substantial barrier in the medical and food industries. Hence, while antibiotics are ineffective in eradicating P. aeruginosa biofilm, scientists have explored alternate strategies, including the utilization of natural compounds as a novel treatment option. To this end, curcumin, carvacrol, thymol, eugenol, cinnamaldehyde, coumarin, catechin, terpinene-4-ol, linalool, pinene, linoleic acid, saponin, and geraniol are the major natural compounds extensively utilized for the management of the P. aeruginosa biofilm community. Noteworthy, the exact interaction of natural compounds and the biofilm of this bacterium is not elucidated yet; however, the interference with the quorum sensing system and the inhibition of autoinducer production in P. aeruginosa are the main possible mechanisms. Noteworthy, the use of different drug platforms can overcome some drawbacks of natural compounds, such as insolubility in water, limited oral bioavailability, fast metabolism, and degradation. Additionally, drug platforms can deliver different antibiofilm agents simultaneously, which enhances the antibiofilm potential of natural compounds. This article explores many facets of utilizing natural compounds to inhibit and eradicate P. aeruginosa biofilms. It also examines the techniques and protocols employed to enhance the effectiveness of these compounds.

The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms’ resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, β–pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.

Staphylococcus aureus is an important pathogen due to its ability to form strong biofilms and antibiotic resistance. Biofilms play an important role in bacterial survival against the host immune system and antibiotics. Natural compounds (NCs) have diverse bioactive properties with a low probability of resistance, making them promising candidates for biofilm control. NC such as curcumin, cinnamaldehyde, carvacrol, eugenol, thymol, citral, linalool, 1,8-cineole, pinene, cymene, terpineol, quercetin, and limonene have been widely utilized for the inhibition and destruction of S. aureus biofilms. NCs influence biofilm formation through several procedures. Some of the antibiofilm mechanisms of NCs are direct bactericidal effect, disrupting the quorum sensing system, preventing bacteria from aggregation and attachment to surfaces, reducing the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), interfering with sortase A enzyme, and altering the expression of biofilm-associated genes such as icaADBC, agr, and sarA. Furthermore, these compounds affect extracellular polymeric substances (EPS) and their components, such as polysaccharide intercellular adhesin (PIA) and eDNA. However, some disadvantages, such as low water solubility and bioavailability, limit their clinical usage. Therefore, scientists have considered using nanotechnology and drug platforms to improve NC’s efficacy. Some NC, such as thymol and curcumin, can also enhance photodynamic therapy against S. aurous biofilm community. This article evaluates the anti-biofilm potential of NC, their mechanisms of action against S. aureus biofilms, and various aspects of their application.

Streptococcus mutans is recognized as one of the leading causes of dental caries, and biofilm formation by this bacterium plays a key role in dental plaque development and caries progression. Given the increasing resistance of bacteria to antibiotics and the adverse effects of some synthetic antimicrobials, the search for natural alternatives has received increasing attention. The recently published studies have demonstrated that natural compounds (NCs) such as curcumin, cinnamaldehyde, eugenol, thymol, carvacrol, epigallocatechin gallate, farnesol, catechin, inulin, menthol, apigenin, myricetin, oleanolic acid, and resveratrol, have notable antimicrobial properties and can effectively inhibit the growth of Streptococcus mutans. NCs can disrupt bacterial membrane integrity, leading to cell death, and possess the capability to inhibit acid production, which is a key factor in caries development. NCs can also interfere with bacterial adhesion to surfaces, including teeth. The attachment inhibition is achieved by decreasing the expression of adhesion factors such as gtfs, ftf, fruA, and gbpB. NCs can disrupt bacterial metabolism, inhibit biofilm formation, disperse existing biofilm, and interfere with quorum sensing and two-component signal transduction systems. Moreover, novel drug delivery platforms were used to enhance the bioavailability and stability of NCs. Studies have also indicated that NCs exhibit significant efficacy in combination therapies. Notably, curcumin has shown promising results in photodynamic therapy against S. mutans. The current review article analyzes the mechanisms of action of various NCs against S. mutans and investigates their potential as alternative or complementary therapeutic options for managing this bacterium and dental caries.

CRS with nasal polyps (CRSwNP) is a multifactorial disease, and various etiological factors like bacterial superantigens are known to develop this disease. Recent studies reported that Staphylococcus aureus nasal colonization was detected in 67% of the patients with CRSwNP. Moreover, it was reported that specific IgE against S. aureus enterotoxins are discovered in almost half of the nasal tissue homogenates from nasal polyps. Thus, investigations have highlighted the role of staphylococcal enterotoxins, especially enterotoxin B (SEB), in pathogenesis of CRSwNP. The destruction of mucosal integrity was reported as a main SEB-related pathogenic mechanisms in CRSwNP. SEB activates Toll Like Receptor 2 and triggers the production of pro-inflammatory cytokines; furthermore, it induces reactive oxygen species and endoplasmic reticulum stress-induced inflammation that may cause epithelial cell integrity disruption and enhance their permeability. SEB-induced Type 2/Th2 pathway results in degranulation of eosinophils, cationic proteins production, and localized eosinophilic inflammation. Furthermore, SEB may be involved in the expression of RORC and HIF-1α in Tregs and by maintaining the inflammation in sinonasal mucosa that could have a main role in the pathogenesis of nasal polyposis. Different in vitro findings were confirmed in animal studies; however, in vivo analysis of SEB-induced nasal polyps and CRS remains unfulfilled due to the lack of appropriate animal models. Finally, after elucidating different aspects of SEB pathogenesis in CRSwNP, therapeutic agents have been tested in recent studies with some encouraging results. The purpose of this article is to summarize the most important findings regarding SEB-induced CRS and nasal polyposis.

Background: The emergence of ciprofloxacin‐resistant bacteria is a serious challenge worldwide, bringing the need to find new approaches to manage this bacterium. Bacteriophages (phages) have been shown inhibitory effects against ciprofloxacin‐resistance bacteria; thus, ciprofloxacin resistance or tolerance may not affect the phage's infection ability. Additionally, researchers used phage‐ciprofloxacin combination therapy for the inhibition of multidrug‐resistant bacteria.Results: The sublethal concentrations of ciprofloxacin could lead to an increase in progeny production. Antibiotic treatments could enhance the release of progeny phages by shortening the lytic cycle and latent period. Thus, sublethal concentrations of antibiotics combined with phages can be used for the management of bacterial infections with high antibiotic resistance. In addition, combination therapy exerts various selection pressures that can mutually decrease phage and antibiotic resistance. Moreover, phage ciprofloxacin could significantly reduce bacterial counts in the biofilm community. Immediate usage of phages after the attachment of bacteria to the surface of the flow cells, before the development of micro‐colonies, could lead to the best effect of phage therapy against bacterial biofilm. Noteworthy, phage should be used before antibiotics usage because this condition may have allowed phage replication to occur first before ciprofloxacin interrupted the bacterial DNA replication process, thereby interfering with the activity of the phages. Furthermore, the phage‐ciprofloxacin combination showed a promising result for the management of Pseudomonas aeruginosa infections in mouse models. Nevertheless, low data are existing about the interaction between phages and ciprofloxacin in combination therapies, especially regarding the emergence of phage‐resistant mutants. Additionally, there is a challenging and important question of how the combined ciprofloxacin with phages can increase antibacterial functions. Therefore, more examinations are required to support the clinical usage of phage‐ciprofloxacin combination therapy.