Abstract
Antimicrobial resistance is an alarming problem, especially due to emergence of methicillin-resistance Staphylococcus aureus (MRSA). World Health Organization (WHO) has already listed MRSA as a top priority pathogen for the development of novel antibacterial agents. Presently, different therapeutic approaches against bacterial infections are in practice which includes targeting bacterial virulence factors, bacteriophage therapy, and manipulation of the microbiome. Natural products have been efficiently used for centuries to combat bacterial infections. Morchella is a natural fungal product which has been reported to possess broad-spectrum biological activities against bacterial infections. Hence, this study was aimed to evaluate the antibacterial efficacy of two macro-fungi against S. aureus, MRSA, and Streptococcus pyogenes (S. pyogenes). The antibacterial potential of both fungal extracts (Morchella esculenta and Morchella conica) was evaluated using disk diffusion and standard broth microdilution methods. The chemical compounds of both fungi were investigated using ultra-performance liquid chromatography mass spectroscopy (UPLC–MS) analysis. All fungal extracts inhibited growth of tested bacteria with inhibitory zone ranging from 10.66 ± 0.3 to 21.00 ± 1.5 mm. The minimum inhibitory concentration (MIC) of tested bacterial growth ranged from 03.33 to 16.0 mg/ml. It was noteworthy that Morchella extracts prevented S. aureus growth in a bactericidal manner with minimal bactericidal concentration (MBC) of 8–16 mg/ml. The extracts were also more effective against MRSA than currently available antibiotics. In conclusion, the growth inhibition of tested bacteria by fungal extracts revealed their potential as antibacterial agents and their compounds may be used as drug candidates.
Similar content being viewed by others
Data availability
All the authors of the study had full access to all data and take responsibility to submit for publication.
References
Abbes S, Trabelsi H, Amouri I, Sallemi H, Nej S, Fatma C, Makni F, Ayadi A (2012) Méthodes d’étude de la sensibilité in vitro de Candida spp. aux antifongiques. Ann Biol Clin (Paris) 70(6):635–642
Aburawi SM, Doro BM, Awad EA (2019) Effect of ciprofloxacin on S. aureus and E. coli growth in presence of vitamin C using cup cut diffusion method. J Pharm Pharmacol 7:473–484
Acay H (2021) Utilization of Morchella esculenta-mediated green synthesis golden nanoparticles in biomedicine applications. Prep Biochem Biotechnol 51(2):127–136
Ahmad MI, Keach JE, Behl T, Panichayupakaranant P (2019) Synergistic effect of α-mangostin on antibacterial activity of tetracycline, erythromycin, and clindamycin against acne involved bacteria. Chin Herb Med 11(4):412–416
Alves MJ, Ferreira IC, Dias J, Teixeira V, Martins A, Pintado M (2012) A review on antimicrobial activity of mushroom (Basidiomycetes) extracts and isolated compounds. Planta Med 78(16):1707–1718
Alves MJ, Ferreira IC, Lourenço I, Castro A, Pereira L, Martins A, Pintado M (2014) Wild mushroom extracts potentiate the action of standard antibiotics against multiresistant bacteria. J Appl Microbiol 116(1):32–38
Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, Harrison LH, Sofair AN, Warnock WD (2002) Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Antimicrob Agents Chemother 46(8):2477–2481
Atila F, Owaid MN, Shariati MA (2021) The nutritional and medical benefits of Agaricus bisporus: a review. J Microbiol Biotechnol Food Sci 2021:281–286
Bala N, Aitken EA, Fechner N, Cusack A, Steadman KJ (2011) Evaluation of antibacterial activity of Australian basidiomycetes macro fungi using a high-throughput 96-well plate assay. Pharm Biol 49(5):492–500
Begum N, Nasir A, Parveen Z, Muhammad T, Ahmed A, Farman S, Jamila N, Shah M, Bibi NS, Khurshid A (2021) Evaluation of the hypoglycemic activity of Morchella conica by targeting protein tyrosine phosphatase 1B. Front Pharmacol 12:1148
Canli K, Benek A, Şenturan M, Akata İ, Altuner EM (2019) In vitro antimicrobial activity of Morchella esculenta and Trametes versicolor. Mantar Dergisi 10(3):28–33
Chassagne F, Cabanac G, Hubert G, David B, Marti G (2019) The landscape of natural product diversity and their pharmacological relevance from a focus on the dictionary of natural products®. Phytochem Rev 18(3):601–622
CLSI (2006). Clinical and Laboratory Standards Institute method for dilution antimicrobial test for bacteria that grow aerobically; approved standard. (Eleventh Edition), approved standard M07-A11.
CLSI (2021) M100 performance standards for antimicrobial susceptibility testing a CLSI supplement for global application. Performance standards for antimicrobial susceptibility testing (2020). Sci Rep 11:16286
De Silva DD, Rapior S, Sudarman E, Stadler M, Xu J, Alias SA, Hyde KD (2013) Bioactive metabolites from macro fungi: ethno pharmacology, biological activities and chemistry. Fungal Divers 62(1):1–40
Doern GV, Jones RN, Pfaller MA, Kugler KC, Group SS (1999) Beach ML (1999) Bacterial pathogens isolated from patients with skin and soft tissue infections: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program (United States and Canada, 1997). Diagn Microbiol Infect Dis 34(1):65–72
Durand GA, Raoult D, Dubourg G (2019) Antibiotic discovery: history, methods and perspectives. Int J Antimicrob Agents 53(4):371–382
Erdoğan Eliuz EA (2021) Antibacterial activity and antibacterial mechanism of ethanol extracts of Lentinula edodes (Shiitake) and Agaricus bisporus (button mushroom). Int J Environ Health Res. https://doi.org/10.1080/09603123.2021.1919292
Etame RME, Mouokeu RS, Poundeu FSM, Voukeng IK, Cidjeu CLP, Tiabou AT, Yaya AJG, Ngane RAN, Kuiate JR, Etoa FX (2019) Effect of fractioning on antibacterial activity of n-butanol fraction from Enantia chlorantha stem bark methanol extract. BMC Complement Altern Med 19(1):1–7
Falagas ME, Siempos II, Vardakas KZ (2008) Linezolid versus glycopeptide or β-lactam for treatment of Gram-positive bacterial infections: meta-analysis of randomised controlled trials. Lancet Infect Dis 8(1):53–66
Ferri M, Ranucci E, Romagnoli P, Giaccone V (2017) Antimicrobial resistance: a global emerging threat to public health systems. Crit Rev Food Sci Nutr 57(13):2857–2876
Gebreyohannes G, Nyerere A, Bii C, Berhe Sbhatu D (2019) Determination of antimicrobial activity of extracts of indigenous wild mushrooms against pathogenic organisms. Evid Based Complement Alternat Med. 2019:6212673
Gil-Gil T, Laborda P, Sanz-García F, Hernando-Amado S, Blanco P, Martínez JL (2019) Antimicrobial resistance: a multifaceted problem with multipronged solutions. Microbiologyopen 8(11):e945
Green KJ, Dods K, Hammer KA (2020) Development and validation of a new microplate assay that utilizes optical density to quantify the antibacterial activity of honeys including Jarrah, Marri and Manuka. Plos One 15(12):e0243246
Hamayun M, Khan SA, Ahmad H, Shin D-H, Lee I-J (2006) Morel collection and marketing: a case study from the Hindu-Kush mountain region of Swat. Pakistan Lyonia 11(2):7–13
Hassan F, Ni S, Becker TL, Kinstedt CM, Abdul-Samad JL, Actis LA, Kennedy MA (2019) Evaluation of the antibacterial activity of 75 mushrooms collected in the vicinity of Oxford, Ohio (USA). Int J Med Mushrooms 21(2):131–141
Hauser AR, Mecsas J, Moir DT (2016) Beyond antibiotics: new therapeutic approaches for bacterial infections. Clin Infect Dis 63(1):89–95
Heleno SA, Stojković D, Barros L, Glamočlija J, Soković M, Martins A, Queiroz MJR, Ferreira IC (2013) A comparative study of chemical composition, antioxidant and antimicrobial properties of Morchella esculenta (L.) Pers. from Portugal and Serbia. Food Res Int 51(1):236–243
Houri H, Kazemian H, Ebrahim-Saraie HS, Taji A, Tayebi Z, Heidari H (2017) Linezolid activity against clinical Gram-positive cocci with advanced antimicrobial drug resistance in Iran. J Glob Antimicrob Resist 10:200–203
Huang M, Zhang S, Zhang M, Ou S, Pan Z (2012) Effects of polysaccharides from Morchella conica on nitric oxide production in lipopolysaccharide-treated macrophages. Appl Microbiol Biotechnol 94(3):763–771
Imöhl M, Fitzner C, Perniciaro S, van der Linden M (2017) Epidemiology and distribution of 10 superantigens among invasive Streptococcus pyogenes disease in Germany from 2009 to 2014. PLoS ONE 12(7):e0180757
Jakubczyk D, Dussart F (2020) Selected fungal natural products with antimicrobial properties. Molecules 25(4):911
Kanayama S, Ikeda F, Okamoto K, Nakajima A, Matsumoto T, Ishii R, Amano A, Matsuzaki K, Matsumoto S (2016) In vitro antimicrobial activity of ozenoxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Streptococcus pyogenes isolated from clinical cutaneous specimens in Japan. J Infect Chemother. 22(10):720–723
Kim KJ, Yu HH, Cha JD, Seo SJ, Choi NY, You YO (2005) Antibacterial activity of Curcuma longa L. against methicillin-resistant Staphylococcus aureus. Phytother Res 19(7):599–604
Kollef M (2005) Antibiotic management of ventilator-associated pneumonia due to antibiotic-resistant gram-positive bacterial infection. Eur J Clin Microbiol Infect Dis 24(12):794–803
Kumar S, Singh S, Kumar V, Datta S, Dhanjal DS, Sharma P, Singh J (2020) Pathogenesis and antibiotic resistance of Staphylococcus aureus. Model organisms for microbial pathogenesis, biofilm formation and antimicrobial drug discovery. Springer, Singapore, pp 99–115
Lee AS, de Lencastre H, Garau J, Kluytmans J, Malhotra-Kumar S, Peschel A, Harbarth S (2018a) Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers 4(1):1–23
Lee SR, Roh H-S, Lee S, Park HB, Jang TS, Ko Y-J, Baek K-H, Kim KH (2018b) Bioactivity-guided isolation and chemical characterization of antiproliferative constituents from morel mushroom (Morchella esculenta) in human lung adenocarcinoma cells. J Funct Foods 40:249–260
Li W, Cai Z-N, Mehmood S, Liang L-L, Liu Y, Zhang H-Y, Chen Y, Lu Y-M (2019) Anti-inflammatory effects of Morchella esculenta polysaccharide and its derivatives in fine particulate matter-treated NR8383 cells. Int J Biol Macromol 129:904–915
Ligon BL (2004) Penicillin: its discovery and early development. Semin Pediatr Infect Dis 15(1):52–7
Lindequist U, Niedermeyer TH, Jülich W-D (2005) The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2(3):285–299
Liu J, Liu G (2018) Analysis of secondary metabolites from plant endophytic fungi. In: Ma Wenbo, Wolpert Thomas (eds) Plant pathogenic fungi and oomycetes. Springer, NY, pp 25–38
Lowy FD (1998) Staphylococcus aureus infections. New Engl J Med 339(8):520–532
McClure J-AM, Lakhundi S, Kashif A, Conly JM, Zhang K (2018) Genomic comparison of highly virulent, moderately virulent, and avirulent strains from a genetically closely-related MRSA ST239 sub-lineage provides insights into pathogenesis. Front Microbiol 9:1531
Mussagy CU, Winterburn J, Santos-Ebinuma VC, Pereira JFB (2019) Production and extraction of carotenoids produced by microorganisms. Appl Microbiol Biotechnol 103(3):1095–1114
Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79(3):629–661
Niederman MS (2001) Impact of antibiotic resistance on clinical outcomes and the cost of care. Crit Care Med 29(4):N114–N120
Niego AG, Rapior S, Thongklang N, Raspé O, Jaidee W, Lumyong S, Hyde KD (2021) Macro fungi as a nutraceutical source: promising bioactive compounds and market value. J Fungi 7(5):397
Nitha B, Janardhanan K (2008) Aqueous-ethanolic extract of morel mushroom mycelium Morchella esculenta, protects cisplatin and gentamicin induced nephrotoxicity in mice. Food Chem Toxicol 46(9):3193–3199
Organization WH (2017) Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. Geneva: WHO; 2017. (Google Scholar there is no corresponding record for this reference)
Pfaller MA, Mendes RE, Duncan LR, Flamm RK, Sader HS (2018) Activity of dalbavancin and comparator agents against Gram-positive cocci from clinical infections in the USA and Europe 2015–16. J Antimicrob Chemother 73(10):2748–2756
Qin H-L, Liu J, Fang W-Y, Ravindar L, Rakesh K (2020) Indole-based derivatives as potential antibacterial activity against methicillin-resistance Staphylococcus aureus (MRSA). Eur J Med Chem 194:112245
Rai A, Prabhune A, Perry CC (2010) Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and their application in antimicrobial coatings. J Mater Chem 20(32):6789–6798
Rai MK, Gaikwad S, Nagaonkar D, dos Santos CA (2015) Current advances in the antimicrobial potential of species of genus Ganoderma (higher Basidiomycetes) against human pathogenic microorganisms. Int J Med Mushrooms 17(10):921–932
Shameem N, Kamili AN, Ahmad M, Masoodi F, Parray JA (2017) Antimicrobial activity of crude fractions and morel compounds from wild edible mushrooms of north western Himalaya. Microb Pathog 105:356–360
Sher H, Aldosari A, Bussmann RW (2015) Morels of Palas Valley, Pakistan: a potential source for generating income and improving livelihoods of mountain communities. Econ Bot 69(4):345–359
Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B, Tenover FC, Zervos MJ, Band JD, White E (1999) Emergence of vancomycin resistance in Staphylococcus aureus. New Engl J Med 340(7):493–501
Su C-a, Xu X-y, Liu D-y, Wu M, Zeng F-q, Zeng M-y, Wei W, Jiang N, Luo X (2013) Isolation and characterization of exopolysaccharide with immunomodulatory activity from fermentation broth of Morchella conica. DARU J Pharm Sci 21(1):1–6
Sulej J, Osińska-Jaroszuk M, Jaszek M, Grąz M, Kutkowska J, Pawlik A, Chudzik A, Bancerz R (2019) Antimicrobial and antioxidative potential of free and immobilised cellobiose dehydrogenase isolated from wood degrading fungi. Fungal Biol 123(12):875–886
Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y (2018) Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18(3):318–327
Tickell KD, Sharmin R, Deichsel EL, Lamberti LM, Walson JL, Faruque A, Pavlinac PB, Kotloff KL, Chisti MJ (2020) The effect of acute malnutrition on enteric pathogens, moderate-to-severe diarrhea, and associated mortality in the Global Enteric Multicenter Study cohort: a post-hoc analysis. Lancet Glob Health 8(2):e215–e224
Vargas-Sinisterra AF, Ramírez-Castrillón M (2021) Yeast carotenoids: production and activity as antimicrobial biomolecule. Arch Microbiol 203(3):873–888
Vieira V, Fernandes Â, Barros L, Glamočlija J, Ćirić A, Stojković D, Martins A, Soković M, Ferreira IC (2016) Wild Morchella conica Pers. from different origins: a comparative study of nutritional and bioactive properties. J Sci Food Agric 96(1):90–98
Vincent J-L, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin M-H, Wolff M, Spencer RC, Hemmer M (1995) The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) study. JAMA 274(8):639–644
Volcão LM, Halicki PB, Bilibio D, Ramos DF, Bernardi E, Da Silva Júnior FMR (2021) Biological activity of aqueous extracts of Southern Brazilian mushrooms. Int J Environ Health Res 31(2):148–159
Wu G, Sun Y, Deng T, Song L, Li P, Zeng H, Tang X (2020) Identification and functional characterization of a novel immunomodulatory protein from Morchella conica SH. Front Immunol. https://doi.org/10.3389/fimmu.2020.559770
Wu H, Chen J, Li J, Liu Y, Park HJ, Yang L (2021) Recent advances on bioactive ingredients of Morchella esculenta. Appl Biochem Biotechnol 193(12):4197–4213
Xu Z (2020) 1, 2, 3-Triazole-containing hybrids with potential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Eur J Med Chem 206:112686
Xu N, Lu Y, Hou J, Liu C, Sun Y (2018) A polysaccharide purified from Morchella conica Pers. prevents oxidative stress induced by H2O2 in human embryonic kidney (HEK) 293T cells. Int J Mol Sci 19(12):4027
Xu W-C, Silverman MH, Yu XY, Wright G, Brown N (2019) Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections. Biorg Med Chem 27(15):3209–3217
Yagnik D, Ward M, Shah AJ (2021) Antibacterial apple cider vinegar eradicates methicillin resistant Staphylococcus aureus and resistant Escherichia coli. Sci Rep 11(1):1–7
Yang C, Meng Q, Zhou X, Cui Y, Fu S (2019) Separation and identification of chemical constituents of Morchella conica isolated from Guizhou Province China. Biochem Syst Ecol 86:103919
Zhang D, Qian Y, Zhang S, Ma P, Zhang Q, Shao N, Qi F, Xie J, Dai C, Zhou R (2019) Alpha-beta chimeric polypeptide molecular brushes display potent activity against superbugs-methicillin resistant Staphylococcus aureus. Sci China Mater 62(4):604–610
Zhu H, Swierstra J, Wu C, Girard G, Choi YH, Van Wamel W, Sandiford SK, van Wezel GP (2014) Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils. Microbiology 160(8):1714–1725
Zhu F, Du B, Bian Z, Xu B (2015) Beta-glucans from edible and medicinal mushrooms: characteristics, physicochemical and biological activities. J Food Compost Anal 41:165–173
Acknowledgements
We acknowledge with thanks Iftekhar Ahmad and Kashif Ahmad for their help and support. The collaboration of the Pharmacology Department of the institute and those who helped us in this research work is appreciated.
Funding
This study was supported by Department of Microbiology, University of Health Sciences Lahore Pakistan.
Author information
Authors and Affiliations
Contributions
FUH and MI designed study and developed the original idea and wrote the manuscript; FUH performed the experiments and wrote the manuscript. MI, SS, UA, and AG contributed with the experiment’s setup. All the authors read and approved the final draft.
Corresponding author
Ethics declarations
Conflict of interest
All the authors declare that they have no competing interests.
Ethical approval
The research project was approved by the University of Health Sciences Lahore, Pakistan Ethical review committee (No: UHS/Reg-21/ERC/1481).
Additional information
Communicated by Erko Stackebrandt.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Haq, F.U., Imran, M., Saleem, S. et al. Investigation of Morchella esculenta and Morchella conica for their antibacterial potential against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes. Arch Microbiol 204, 391 (2022). https://doi.org/10.1007/s00203-022-03003-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00203-022-03003-8