*3.5. Shigella*

*Shigella* is a genus of Gram-negative bacteria. It has four species, *S. flexneri, S. sonnei, S. dysenteriae* and *S. boydii*. These are rod-shaped, non-motile, non-spore forming and facultative anaerobic bacteria [144]. They cause diseases commonly known as shigellosis, characterized by profuse watery diarrhea, fever, abdominal cramps and also bloody dysentery. Ingestion of as low as 100 numbers of these bacteria can cause foodborne disease. These bacteria attack the epithelial cells of the colon of primates only. The resultant inflammation causes high intestinal motility and diarrhea which even leads to dysentery [145]. The virulence of Shiga toxin is like that of verotoxin of *E. coli*, which halts protein synthesis in the host cells [104,146]. In Iran, pomegranate (*Punica granatum*) is commonly used to treat diarrhea. Mahboubi et al. reported that the the extracts of pomegranate were active against *Shigella* [147]. Another study has reported the anti-*Shigella* activity of five plants, e.g., *Thymus vulgaris* L., *Thymus carmanicus* Jalas, *Zataria multiflora* Boiss., *Ziziphora clinopodioides* Lam. and *Ziziphora tenuior* L. Among these *Thymus caramanicus* and *Zataria multiflora* were found comparatively more active having MIC values of 0.78 and 1.56 mg/mL, respectively [148]. In a study by Vuuren et al. 23 traditionally used plants for various ailments including diarrhea, were subjected to antibacterial activity against *Shigella* bateria. Although, all the plants had antibacterial property, *Acacia burkei* Benth. (MIC 0.25 mg/mL), *Acanthospermum glabratum* (DC.) Wild (0.44 mg/mL), *Brachylaena transvaalensis* Hutch. ex E.Phillips & Schweick. (0.5 mg/mL), *Catharanthus roseus* (L.) G.Don (0.41 mg/mL), *Chenopodium ambrosioides* L. (0.5 mg/mL), *Cissampelos hirta* Klotzsch (0.38 mg/mL), *Gymnosporia senegalensis* (Lam.) Loes. (0.63 mg/mL), *Lippia javanica* (0.5 mg/mL), *Mangifera indica* L. (0.25 mg/mL), *Melia azedarach* L. (0.57 mg/mL), *Psidium guajava* L. (0.33 mg/mL), *Sarcostemma viminale* (L.) R.Br. (0.5 mg/mL), *Schotia brachypetala* Sond. (0.58 mg/mL), *Sclerocarya birrea* (A.Rich.) Hochst. (0.34 mg/mL), *Syzygium cordatum* Hochst. ex Krauss (0.43 mg/mL) and *Terminalia sericea* Burch. ex DC. (0.04 mg/mL) were particularly potent [149]. Essential oils are also utilized for foodborne infections caused by *Shigella* [150,151].

### *3.6. Listeria monocytogenes*

*Listeria monocytogenes* (*L. monocytogenes*), a Gram-positive, non-spore-forming, facultative anaerobe widely a ffecting food, meat, poultry and seafood [152]. This pathogen grows between 0.4 and 50 ◦C [104]. The virulence factors of *L. monocytogenes* include the production of beta hemolysin, catalase and superoxide dismutase. It has been implicated in foodborne outbreaks [153]. This microbe can survive refrigeration, high salt content and low pH [154]. These properties enable *L. monocytogenes* to contaminate food even after food postprocessing [155]; *L. monocytogenes* being a foodborne pathogen is

challenged with extracts and compounds derived from medicinal plants. In a study by Yoon et al. in South Korea, 69 herbal extracts were tested for inhibition of *L. monocytogenes*. Psoraleae Semen and Sophorae Radix extracts were found potent in their study [156]. Attachment of *L. monocytogenes* to the human intestinal epithelium and its subsequent invasion results in listeriosis. Motility, lecithinase and hemolysin production are the major virulence factors of this pathogen. The virulence factors, i.e., motility, lecithinase and hemolysin production were also decreased. Furthermore, the expression of the virulence genes was downregulated by cinnamaldehyde, carvacrol and thymol more than 3-folds [157,158]. The essential oils are reported to possess antilisterial activity. Essential oils of *Zataria multiflora* Boiss. from Turkey [159], *Carum copticum* (L.) Benth. & Hook.f. ex C.B.Clarke from Iran [160], *Thymus capitatus* (L.) Hoffmanns. & Link from Tunisia [161], *Cymbopogon citratus* D.C. Stapf. from Brazil [162], *Eryngium foetidum L.* from Italy [163] have been reported to have the potential of inhibiting *L. monocytogenes*.

### *3.7. Clostridium spp.*

*Clostridium botulinum* (*C. botulinum*) is a Gram-positive, rod-shaped, motile, obligate anaerobe [164]. It is a spore-forming bacterium and produces a neurotoxin known as botulinum [165]. It causes a foodborne disease known as foodborne botulism. This happens after ingestion of the preformed toxin produced by *C. botulinum*. The major virulence factor is toxin production [166]. Seven types of toxins have been identified. These are named as A–G. Among these, A, B and E toxin types are associated with foodborne illness. The symptoms of foodborne botulinum are blurred vision, dry mouth, nausea, vomiting, abdominal cramps and difficulty in swallowing [167,168]. Toosendanin, a natural compound, prevents botulinum in animals [169].

*C. perfringens*, a Gram-positive, spore-forming bacteria has a widespread anaerobic environmental distribution including soil, foodstuff and is part of human flora [170]. Extracts from traditionally important medicinal plants including *Psidium guajava* L., *Haematoxylum brasiletto* H.Karst. and *Euphorbia prostrata* Aiton were found highly effective against *C. perfringens* type A [171]. Likewise, essential oils from *Satureja montana* L. tested against *C. perfringens* type A at a concentration of 1.56%, showed inhibitory activity causing structural damage and cell lysis. Moreover, a synergistic effect between NaNO2 and *Satureja montana* EOs was observed and the findings sugges<sup>t</sup> the potential combined use of savory essential oil and minimal amounts of the synthetic additive, NaNO2 to control *C. perfringens*[172]. The natural product, berberine demonstrated efficacy towards the *C. perfringens* disease based on significantly decreased mortality and lesion scores at 1.0 mL/L, in vitro [173]. Extracts from several plants *Pueraria thunbergiana* (Siebold & Zucc.) Benth., *Astragalus membranaceus* (Fisch.) Bunge, *Eucommia ulmoides* Oliv., *Coptis japonica* (Thunb.) Makino, *Akebia quinata* (Houtt.) Decne. and *Rhus chinensis* Mill. exhibited considerable activity against *C. perfringens* [174].

### *3.8. Bacillus cereus*

*B. cereus,* a Gram-positive spore-forming bacterium, is frequently implicated in foodborne infections. Among the pathogenic aspects of the bacterium is the production of tissue-damaging exo-enzymes. The bacterium secretes toxins including hemolysins, phospholipases, emesis-inducing toxins and proteases [175]. In the in vitro antibacterial assay against *B. cereus*, the extract of *Dryopteris erythrosora* (D.C. Eaton) Kuntze exhibited an MIC of 0.0156 mg/mL, followed by *Siegesbeckia glabrescens* (SG) Makino leaf (0.0313 mg/mL), *Morus alba* L. bark (0.0313 mg/mL), *Carex pumila* Thunb. root (0.0625 mg/mL) and *Citrus paradisi* Macfad. seed (0.0625 mg/mL) extracts. The combined inhibitory effects of extracts against *B. cereus* were also determined. A combination of *D. erythrosora* and *C. pumila* extracts showed a partial synergistic inhibition, with a fractional inhibitory concentration index of 0.75. The single and combined inhibitory activities of selected plant extracts against *B. cereus* in reconstituted infant rice cereal were also investigated and showed the MICs of *S. glabrescens*, *M. alba*, *D. erythrosora* and *C. pumila* extracts against *B. cereus* as 1.0, 2.0, 2.0 and 8.0 mg/mL, respectively [176]. The plant extracts of *Rhus coriaria* L. and *Hipiscus sabdari*ff*a* L. were investigated against six presumptive *Bacillus*

*cereus* isolates that were isolated from 49 samples of food, soil, manure and eggshells in Amman, Jordan. It was observed that the inhibition of the growth of bacteria was proportional to the increase in extract concentrations. Complete inhibition of the growth was demonstrated at the highest concentrations. The authors concluded that *Rhus coriaria* and *Hibiscus sabdari*ff*a* have the potential to be used as food preservatives against wider spectra of spoilage microorganisms in food [177].

### *3.9. Vibrio cholerae*

*V. cholerae*, a Gram-negative curved rod from family *Vibrionaceae* has two major virulence factors including cholera toxin, causing profuse rice-watery diarrhea and toxin-coregulated pilus that is mediated in intestinal colonization [178]. Cholera caused by toxigenic *V. cholerae* is a major public health problem particularly in less developed regions of the world with poor sanitation facilities [179]. The extracts of *Ocimum basilicum* L., *Opuntia ficus-indica* (L.) Mill., *Acacia farnesiana* (L.) Willd. and *Artemisia ludoviciana* Nutt. were found active against *V. cholera*, with MBCs values ranging from 0.5–3.0-mg/mL [180]. Recently, solvent-based extracts from red chili, sweet fennel and white pepper were reported to inhibit cholera toxin production. Further, capsaicin the active ingredient of chili prevented the synthesis of cholera toxin in different strains of *V. cholerae*. Capsaicin declined the expression of virulent genes (*ctxA, tcpA* and *toxT)* ye<sup>t</sup> increased the expression of *hns* gene that transcribes a global prokaryotic gene regulator (H-NS) [181]. Solvents based extracts from 32 Mexician plants were evaluated for their inhibitory effects against *V. cholera* strains (O1, O139). Among these, *Acacia farnesiana* and *Artemisia ludoviciana* ethanolic extracts were more effective with minimum Bactericidal Concentrations of 4.0–7.0 and 4.0–6.0-mg/mL respectively [182]. In another study, the extracts of *Terminalia chebula* Retz. and *Syzygium cumini* (L.) Skeels exhibited considerable activity against *V. cholerae*, *Aeromonas hydrophila* and *Bacillus subtilis*, with MBCs (0.25–4 mg/mL). These results favor the use of ethnopharmacological important plants in the managemen<sup>t</sup> of diarrhea, especially those associated with cholera [183].

### **4. Plant Extracts and Phytochemicals against Viruses Causing Foodborne Diseases**
