Chitosan propolis nanocomposite alone or in combination with apramycin: an alternative therapy for multidrug-resistant Salmonella Typhimurium in rabbits: in vitro and in vivo study
Introduction. The emergence of multidrug-resistant Salmonella Typhimurium strains has increased the need for safe, alternative therapies from natural sources with antibacterial properties.
Hypothesis/Gap Statement. There are no published data regarding the use of chitosan propolis nanocomposite (CPNP) either alone or in combination with antibiotics as antimicrobials against S. Typhimurium, especially in Egypt.
Aim. This study evaluated the antibacterial activities of five antimicrobials [apramycin, propolis, chitosan nanoparticles (CNPs), chitosan propolis nanocomposite (CPNP) and CPNP +apramycin] against ten virulent and multidrug-resistant (MDR) S. Typhimurium field strains recovered from diarrheic rabbits through in vitro and in vivo study.
Methodology. The expression levels of three virulence genes of S. Typhimurium strains were determined by quantitative reverse-transcription PCR (RT-qPCR) after exposure to sub-inhibitory concentrations of apramycin, propolis, CNPs, CPNP alone, and CPNP +apramycin. Additionally, 90 New Zealand rabbits were divided into control and experimentally S. Typhimurium-infected groups. The infected rabbits were orally administered saline solution (infected–untreated); 10 mg apramycin/kg (infected–apramycin-treated); 50 mg propolis/kg (infected–propolis-treated); 15 mg CPNP/kg (infected–CPNP-treated) and 15 mg CPNP +10 mg apramycin/kg (infected–CPNP +apramycin-treated) for 5 days.
Results. The RT-qPCR analysis revealed different degrees of downregulation of all screened genes. Furthermore, the treatment of infected rabbits with CPNP or CPNP +apramycin significantly improved performance parameters, and total bacterial and Salmonella species counts, while also modulating both oxidative stress and altered liver and kidney parameters.
Conclusion. This work demonstrates the use of CPNP alone or in combination with apramycin in the treatment of S. Typhimurium in rabbits.
ForshellLP, WierupM. Salmonella contamination: a significant challenge to the global marketing of animal food products. Rev Sci Tech2006; 25:541–554 [PubMed]
Abd El-HamidMI, AwadNFS, HashemYM, Abdel-RahmanMA, AbdelazizAM et al.In vitro evaluation of various antimicrobials against field avian Mycoplasma gallisepticum and Mycoplasma synoviae isolates in Egypt. Poult Sci2019; 98:6281–6288 [View Article] [PubMed]
BendaryMM, IbrahimD, MosbahRA, MosallamF, HegazyWAH et al. Thymol nanoemulsion: A new therapeutic option for extensively drug resistant foodborne pathogens. Antibiotics2021; 10:25
SiheriW, AleneziS, TusiimireJ, WatsonDG. The chemical and biological properties of propolis. In Alvarez-SuarezJ. eds Bee Products - Chemical and Biological Properties Cham: Springer; 2017 pp 137–178
RazavizadehBM, NiazmandR, HajinezhadS, AkbariE. Physicochemical and antimicrobial properties and determination of phenols and flavonoids content of propolis from bee hives in Khorasan Razavi Province. J res Innovation Food Sci Technol2020; 9:27–40
AfrouzanH, AmiriniaC, MirhadiSA, EbadollahiA, VasejiN et al. Evaluation of antimicrobial activity of propolis and nanopropolis against Staphylococcus aureus and Candida albicans. Afr J Microbiol Res2012; 2:421–425
WeiS, ChingYC, ChuahCH. Synthesis of chitosan aerogels as promising carriers for drug delivery: A review. Carbohydr Polym2020; 231:115744 [View Article] [PubMed]
Vilar JuniorJC, RibeauxDR, Alves da SilvaCA, De Campos-TakakiGM. Physicochemical and antibacterial properties of chitosan extracted from waste shrimp shells. Int J Microbiol2016; 2016:5127515 [View Article] [PubMed]
KimS. Competitive biological activities of chitosan and its derivatives: Antimicrobial, antioxidant, anticancer and anti-Inflammatory activities. Int J Polym Sci2018; ID:1708172
IvanovaDG, YanevaZL. Antioxidant properties and redox-modulating activity of chitosan and its derivatives: Biomaterials with application in cancer therapy. Biores Open Access2020; 9:64–72 [View Article] [PubMed]
OngTH, ChitraE, RamamurthyS, LingCCS, AmbuSP. Cationic chitosan-propolis nanoparticles alter the zeta potential of S. epidermidis, inhibit biofilm formation by modulating gene expression and exhibit synergism with antibiotics. PLoS ONE2019; 14:e0213079 [View Article] [PubMed]
El-SheikhSMA, Abd El-AlimA, IbrahimHAF, MobarezEA, El-MasryDMA et al. Preparation, characterization and antibacterial activity of chitosan nanoparticle and chitosan-propolis nanocomposite. Adv Anim Vet Sci2019; 7:183–190
LiuB, ZhouX, ZhangL, LiuW, DanX. Development of a novel multiplex PCR assay for the identification of Salmonella enterica typhimurium and enteritidis. Food Control2012; 27:87–93 [View Article]
HanesDE, RoblMG, SchneiderCM, BurrDH. New Zealand White Rabbit as a nonsurgical experimental model for salmonella enterica gastroenteritis. Infect Immun2001; 69:6523–6526 [View Article] [PubMed]
ISO, 6579 Microbiology of food and animal feeding stuffs-horizontal method for the detection of salmonella spp. International standard; 2017
EMA The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit. Committee for veterinary medicinal products, apramycin; 1999
NassarSA, MohamedAH, SoufyH, NasrSM, MahranKM. Immunostimulant effect of Egyptian propolis in rabbits. Sci World J2012901516
SevenPT, SevenI, KarakusS, MutluS, ArkaliG et al. Turkish propolis and its nano form can amelioratethe side effects of cisplatin, which is a widely used drug in the treatment of cancer. Plants2020; 9:E1075
Reagan-ShawS, NihalM, AhmadN. Dose translation from animal to human studies revisited. official publication of the Federation of American Societies for Experimental Biology. FASEB J2008; 22:659–661
OrsiRO, FernandesA, BankovaV, SforcinJM. The effects of Brazilian and Bulgarian propolis in vitro against Salmonella Typhi and their synergism with antibiotics acting on the ribosome. Nat Prod Res2012; 26:430–437 [View Article] [PubMed]
KrolW, SchellerS, ShaniJ, PietszG, CzubaZ. Synergistic effect of ethanolic extract of propolis and antibiotics on the growth of Staphylococcus aureus. Arzneimittelforschung1993; 43:607–609 [PubMed]
KaliaP, KumarNR, HarjaiK. Studies on the therapeutic effect of propolis along with standard antibacterial drug in Salmonella enterica serovar Typhimurium infected BALB/c mice. BMC Complement Altern Med2016; 16:485 [View Article] [PubMed]
SeoHW, SuhJH, KyungJ-S, JangKH, SoS-H. Subacute oral toxicity and bacterial mutagenicity study of a mixture of Korean red ginseng (Panax ginseng C.A. Meyer) and Salvia plebeia R. Br. Extracts. Toxicol Res2019; 35:215–224 [View Article]
PapamichalisP, ArgyrakiK, PapamichalisM, LoukopoulosA, DalekosGN et al. Salmonella enteritidis infection complicated by acute myocarditis: A case report and review of the literature. SAGE-Hindawi Access to Cardiol Res Pract2011574230
KupczyńskiR, PiaseckiT, BednarskiM, ŚpitalniakK, Budny-WalczakA. Application of herbs and propolis in rabbits with chronic diarrhea. Turk J Vet Anim Sci2016; 40:344–351 [View Article]
El-DensharyES, AljawishA, El-NekeetyAA, HassanNS, SalehRH et al. Possible synergistic effect and antioxidant properties of chitosan nanoparticles and quercetin against carbon tetrachloride-induce hepatotoxicity in rats. Soft Nanoscience Letters2015; 5:36–51
AbdulgaforAB, OwainMS, HasanMS, HusseinMA, AboudQM et al. Liver, kidney function tests and oxidative damage during and after treatment of Salmonella Typhimurium infection in experimental local rabbits. IJPQA2018; 9:377–380
Do NascimentoTG, Da SilvaPF, AzevedoLF, Da RochaLG, De Moraes PortoICC. Polymeric nanoparticles of brazilian red propolis extract: Preparation, characterization, antioxidant and leishmanicidal activity. Nanoscale Res Lett2016; 11:301 [View Article] [PubMed]
Tatli SevenP, YilmazS, SevenI, CerciIH, AzmanMA et al. Effects of propolis on selected blood indicators and antioxidant enzyme activities in broilers under heat stress. Acta Vet Brno2009; 78:75–83
TorresE, MarínV, AburtoJ, BeltránHI, ShiraiK. Enzymatic modification of chitosan with quercetin and its application as antioxidant edible films. Prikl Biokhim Mikrobiol2012; 48:175–182 [PubMed]
MurugkarHV, RahmanH, DuttaPK. Distribution of virulence genes in Salmonella serovars isolated from man & animals. Indian J Med Res2003; 117:66–70 [PubMed]
HuehnS, La RagioneRM, AnjumM, SaundersM, WoodwardMJ. Virulotyping and antimicrobial resistance typing of Salmonella enterica serovars relevant to human health in Europe. Foodborne Pathog Dis2010; 7:523–535 [View Article] [PubMed]
ColomK, PèrezJ, AlonsoR, Fernández-AranguizA, LariňoE. Simple and reliable multiplex PCR assay for detection of blaTEM, bla (SHV) and blaOXA-1 genes in Enterobacteriaceae. FEMS Microbiol Lett2003; 223:147–151 [View Article] [PubMed]
YangX, BrisbinJ, YuH, WangQ, YinF et al. Selected lactic acid-producing bacterial isolates with the capacity to reduce Salmonella translocation and virulence gene expression in chickens. PLoS ONE2014; 9:e93022
Chitosan propolis nanocomposite alone or in combination with apramycin: an alternative therapy for multidrug-resistant Salmonella Typhimurium in rabbits: in vitro and in vivo study