*4.1. Antimicrobial Activity*

In the past few decades, the microbial infection has become a major health issue across the world, due to its continuously evolving nature and ability to develop resistance against the existing regime [64]. Therefore, search for a strong alternative candidate that can kill or inhibit multidrug resistance microbes is needed [88]. Metal nanoparticles (MNPs) are known to possess potent antimicrobial activity against a wide variety of microbes, including bacteria (Gram-negative and Gram-positive) and fungi, via their photodynamic effects and strong oxidative stress [89]. Furthermore, the direct physical contact of MNPs to bacterial membrane results in the release of intercellular material, loss of cell membrane integrity, and cell death [88]. In literature, several reports are offered on MNPs' (AgNPs, AuNPs, ZnSNPs) exhibiting bactericidal activity. However, only a few reports focus on the support of their antifungal and antibacterial activity with appropriate mechanisms [88–91]. Moreover, many reports available in literature that favor the mechanism involved in bacterial and fungi cells are almost similar.

In the year 2009, Nithya and Ragunathan synthesized AgNPs (5–50 nm, spherical) derived from *Pleurotus sajor-caju* fungi as the starting material and evaluated their bactericidal activity against the both Gram-negative (*Pseudomonas aeruginosa*, *E. coli*) and Gram-positive (*S. aureus*) bacteria. Authors claimed that the inhibitory action of AgNPs was attributed to the generation of Ag<sup>+</sup> ions by NPs that resulted in DNA damage, protein denaturation, enzymes inhibitions [32]. Two years later, in 2011, Bhat et al. also fabricated AgNPs (20 ± 5 nm, spherical) using *P. florida* mushroom, and studied their antibacterial activity against *S. aureus, Salmonella typhi, Providencia alcalifaciens,* and *Proteus mirabilis*. The prepared NPs show higher activity against the Gram-positive microbes than Gram-negative, especially in the case of *P. mirabilis* [33]. A similar kind of study was presented by Shivashankar et al. (2013) using AgNPs derived from *P. pulmonarius*, *P. djamor*, and *Hypsizygus (pleurotus) ulmarius* as the precursors [40,41].

Yehia and Sheikh (2014) synthesized AgNPs (4–15 nm, spherical) derived from *P. ostreatus* extracted via the green synthesis route and evaluated their antifungal activity toward the various *Candida* species, i.e., *C. tropicalis*, *C. albicans*, *C. parapsilosis*, *C. krusei*, and *C. glabrata*. The (minimum inhibitory concentration) MIC (IC80) results demonstrated that AgNPs showed higher toxicity against all of the *candida* species (5–28 µg/mL) than the amphotericin B (5–8 µg/mL) and fluconazole (13–33 µg/mL) [36]. The tiny size and capping ability of the bioactive white NPs derived from *P. tuber-regium* extract and silver nitrate showed higher therapeutic efficacy against the various diseases and disorders [61]. Devi and Joshi (2015) synthesized AgNPs derived from three different endophytic fungi, i.e., *Aspergillus niger*, *Aspergillus tamarii*, and *Penicillium ochrochloron* isolated from the ethnomedicinal plant *Potentilla fulgens*

leaves via the green synthesis method. The electron microscopy results revealed that all of the AgNPs derived from different fungi were spherically shaped. However, NPs synthesized from *A. tamarii* showed the smallest size (~3.5 nm) than *A. niger* (~8.7 nm) and *P. ochrochloron* (~7.7 nm), respectively [74]. In the year 2018, Bawadekji et al. fabricated Au NPs (~22.9 nm, spherical) from *P. ostreatus* extract and evaluated their antimicrobial activity toward the bacteria *Enterococcus faecalis*, *E. coli*, *Klebsiella pneumonia*, *S. aureus*, *P. aeruginosa*, and *C. albicans*. The results demonstrated that synthesized NPs showed significant toxicity against *C. albicans*, *P. aeruginosa,* and *S. aureus*. In contrast, no toxicity was observed in the case of *E. faecalis*, *E. coli*, and *K. pneumonia* [54].

Acay and Baran (2019) reported the green synthesis of AgNPs derived from *Pleurotus eryngii* (PE) extract and their antimicrobial activity against the various human pathogen microorganisms, such as *E. coli*, *S. aureus*, *Streptococcus pyogenes*, *P. aeruginosa*, and *C. albicans*. The authors used drug vancomycin, colistin, and fluconazole as the control over the gram-positive, gram-negative, and fungus microorganisms. The observed MIC values for *S. aureus*, *E. coli*, *S. pyogenes*, *C. albicans*, and *P. aeruginosa* were 0.035, 0.07, 0.018, 0.07, and 0.035 mg/L, respectively. Authors claimed that AgNPs derived from (PE) *Pleurotus eryngii* extract could be used as a better alternative, as an antibiotic, compared to the other silver nitrates and antibiotics [45]. After that, Debnath et al. (2019) also fabricated AgNPs from *Pleurotus giganteus* and analyzed their antibacterial activity [51]. The TiO<sup>2</sup> NPs mediated from extract of *P. djamor* exhibited significant bactericidal activity against human pathogenic bacteria with maximum zone of inhibition *P. fluorescens* (33 ± 0.2 mm), *Corynebacterium diphtheria* (32 ± 0.1 mm), *S. aureus* (32 ± 0.4 mm), and showed higher levels of the inhibitory effect [44]. The *P. djamor* ZnONPs showed a maximum zone of inhibition against *C. diphtheriae* (28.6 ± 0.3 mm), *P. fluorescens* (27 ± 0.5 mm), and *S. aureus* (26.6 ± 1.5 mm) [43]. The general mechanism of microbial cell death is summarized, as below and in Figure 3.

**Figure 3.** Graphical representation of mechanism showing anticancer and antimicrobial activity.
