Antimicrobial Natural Products Research Articles

Comparative study of a commercial formula containing natural antimicrobials versus oral cephalexin or topical chlorhexidine-miconazole therapies for treating superficial pyoderma in dogs.

Chronic and recurrent pyoderma in dogs is driving a growing interest in natural antimicrobial products that offer minimal adverse effects and avoid antibiotic resistance. Evaluate the safety and efficacy of dermatological products with antimicrobial peptides and plant extracts, comparing them to chlorhexidine + miconazole and cephalexin therapy for superficial pyoderma in dogs. Forty-five dogs with superficial pyoderma underwent clinical, cytopathological and microbiological diagnosis, and were randomly assigned to Group 1 (G1) treated with shampoo (two weekly baths) and lotion (twice daily on the affected areas) containing natural antimicrobials; Group 2 (G2) treated with two weekly baths using a therapeutic shampoo containing 2% chlorhexidine and 2.5% miconazole; or Group 3 (G3) treated with oral cephalexin 30 mg/kg twice daily. Staphylococcus spp. strains were identified using matrix-assisted laser desorption ionisation-time of flight mass spectrometry and pruritus Visual Analog Scale (PVAS)/lesion scores were evaluated on Day (D)0, D7, D14, D21 and D28. Statistical differences (p < 0.05) were noted between D0 and D28 in PVAS values and lesion scores for all groups. G1 had lower PVAS scores than other groups on D7 and D14 (p < 0.05) and lower lesion scores than G3 on D7. By D28, G1 and G3 had lower lesion scores than G2. Notably, G1 and G2 had no adverse effects, while 26% of G3 patients experienced gastrointestinal issues during therapy. This preliminary investigation of the new product (G1) suggests that it is effective, safe and a promising topical treatment for managing superficial pyoderma in dogs, offering an alternative to systemic antibiotics and topical antiseptic treatments.

Large-scale investigation for antimicrobial activity reveals novel defensive species across the healthy skin microbiome.

The human skin microbiome constitutes a dynamic barrier that can impede pathogen invasion by producing antimicrobial natural products. Gene clusters encoding for production of secondary metabolites, biosynthetic gene clusters (BGCs), that are enriched in the human skin microbiome relative to other ecological settings, position this niche as a promising source for new natural product mining. Here, we introduce a new human microbiome isolate collection, the EPithelial Isolate Collection (EPIC). It includes a large phylogenetically diverse set of human skin-derived bacterial strains from eight body sites. This skin collection, consisting of 980 strains is larger and more diverse than existing resources, includes hundreds of rare and low-abundance species, and hundreds of unique BGCs. Using a large-scale co-culture screen to assess 8,756 pairwise interactions between skin-associated bacteria and potential pathogens, we reveal broad antifungal activity by skin microbiome members. Integrating 287 whole isolate genomes and 268 metagenomes from sampling sites demonstrates that while the distribution of BGC types is stable across body sites, specific gene cluster families (GCFs), each predicted to encode for a distinct secondary metabolite, can substantially vary. Sites that are dry or rarely moist harbor the greatest potential for discovery of novel bioactive metabolites. Among our discoveries are four novel bacterial species, three of which exert significant and broad-spectrum antifungal activity. This comprehensive isolate collection advances our understanding of the skin microbiomes biosynthetic capabilities and pathogen-fighting mechanisms, opening new avenues towards antimicrobial drug discovery and microbiome engineering.

Comparison of matrix metalloproteinase levels in periodontal pockets treated with chlorhexidine and propolis

Natural antimicrobial products are attracting interest in the treatment of periodontal diseases due to their minimal or nonexistent side effects. Propolis, a complex resin content produced by bees, has drawn particular interest for its antibacterial effects, including inhibitory effects on periodontopathogenic bacterial species. This study compared the effects of propolis, a natural product, and chlorhexidine, the gold standard antimicrobial agent, on MMP-1 and MMP-9 levels in gingival crevicular fluid (GCF). Subgingival irrigations of chlorhexidine and propolis solutions were performed in selected deep periodontal pockets of periodontitis patients along with scaling and root planing. The treatment protocol was administered three times at one-month intervals starting from the initial day of the study. GCF MMP-1 and MMP-9 levels, along with clinical periodontal parameters, were evaluated before and after treatment. The study results showed that a statistically significant decrease in clinical periodontal parameters in both groups (p&amp;lt;0.001). Biochemical analysis revealed a statistically significant decrease in levels of GCF MMP-1 and MMP-9 in both groups (p&amp;lt;0.005). Additionally, the decrease in GCF MMP-1 levels was found to be significantly greater in the propolis group compared to the chlorhexidine group (p&amp;lt;0.001).

The Molecular Mechanisms and Therapeutic Potential of Cranberry, D-Mannose, and Flavonoids against Infectious Diseases: The Example of Urinary Tract Infections.

The treatment of infectious diseases typically includes the administration of anti-infectives; however, the increasing rates of antimicrobial resistance (AMR) have led to attempts to develop other modalities, such as antimicrobial peptides, nanotechnology, bacteriophages, and natural products. Natural products offer a viable alternative due to their potential affordability, ease of access, and diverse biological activities. Flavonoids, a class of natural polyphenols, demonstrate broad anti-infective properties against viruses, bacteria, fungi, and parasites. Their mechanisms of action include disruption of microbial membranes, inhibition of nucleic acid synthesis, and interference with bacterial enzymes. This review explores the potential of natural compounds, such as flavonoids, as an alternative therapeutic approach to combat infectious diseases. Moreover, it discusses some commonly used natural products, such as cranberry and D-mannose, to manage urinary tract infections (UTIs). Cranberry products and D-mannose both, yet differently, inhibit the adhesion of uropathogenic bacteria to the urothelium, thus reducing the likelihood of UTI occurrence. Some studies, with methodological limitations and small patient samples, provide some encouraging results suggesting the use of these substances in the prevention of recurrent UTIs. While further research is needed to determine optimal dosages, bioavailability, and potential side effects, natural compounds hold promise as a complementary or alternative therapeutic strategy in the fight against infectious diseases.

Physicochemical and metagenomic analysis of samples from the Roman Baths (Bath, UK) reveals high bacterial and archaeal diversity and a potential for antimicrobial discovery

Antimicrobial resistance of pathogenic bacteria to currently used antibiotics killed an estimated 1.27 million people in 2019 and it is believed that this toll will increase to 10 million per year by 2050. This remains one of the most urgent threats to human health and the hunt for novel antimicrobial natural products (NPs) from microorganisms is essential in efforts to combat this threat, but recent efforts have been unsuccessful. The investigation of extreme ecological niches, such as hot springs, has gained recent interest due to their unique ecosystems, increasing the chance for novel antimicrobial NP discovery. The Roman Baths (Bath) is the UK’s only hot spring and it remains unexplored in terms of microbial diversity. In this study, samples of water, biofilm and sediment were taken from the King’s Spring and the Great Bath, and 16 S rRNA metagenomic sequencing was performed for bacterial and archaeal community exploration. Additionally, samples were used for culture-dependent isolation of antimicrobial NP producing isolates. At the phylum level, data from water samples revealed a shift from an archaeal dominant community in the King’s Spring (Crenarchaeota, Aenigmarchaeota and Nanoarchaeota) to bacteria in the Great Bath (Cyanobacteria and Proteobacteria). Archaea were still present in the biofilm and sediment of the hot spring but consistently the bacterial phyla Cyanobacteria, Bacteroidota, Proteobacteria and Nitrospirota were dominant at both sites. The antimicrobial NP producing candidate phyla Actinobacteria and Myxococcota were found in all samples. From initial isolation experiments, 297 isolates were purified, of which 15 showed broad spectrum activity against human pathogens, though interestingly these were not from target genera in the Actinobacteria. From these data, there is clear potential for novel NP discovery from the Roman Baths, as has been demonstrated from other thermal hot springs globally.

Nisin as a food preservative: physicochemical, sensory properties and antimicrobial activity in Mexican tomato sauce

SummaryBiopreservation is a technique that utilises natural microbiota and antimicrobial products to extend the shelf life of food in a controlled manner. Nisin, bacteriocins, is used commonly in meat and dairy items and is acknowledged as safe by the FDA under the acronym GRAS. Tomato sauce is an essential component of Mexican cuisine but has a limited shelf life. Nisin (0.01%, 0.1% and 0.2%) was used as a preservative to preserve its physicochemical and microbiological properties. The results were compared with those of a control group (with no preservative) and a sample that used potassium sorbate (0.2%) as a preservative. The Mexican tomato sauces were stored at 4, 20 and 35 °C for 180 days to test their stability. The results indicated that the nisin‐preserved Mexican tomato sauces remained stable at all three temperatures for 180 days. In addition, the sauce preserved with 0.01% nisin was preferred by untrained panellists, as it maintained its desirable taste and texture. The sauces preserved with 0.1% and 0.2% nisin exhibited no significant changes in their physicochemical properties. However, after 150 days of preservation, there was a noticeable difference in the antimicrobial activity of the nisin‐containing sauces compared with the sauce with sorbate and the control sauce without any additives. Based on the product's unique characteristics and physicochemical, microbiological and sensory properties, nisin can serve as a natural preservative for Mexican tomato sauces.

Diverse RNA viruses in the venom-related microenvironment of different animal phyla.

Venom is known as the source of natural antimicrobial products. Previous studies have largely focused on the expression of venom-related genes and the biochemical components of venom. With the advent of metagenomic sequencing, many more microorganisms, especially viruses, have been identified in highly diverse environments. Herein, we investigated the RNA virome in the venom-related microenvironment through analysis of a large volume of venom-related RNA-sequencing data mined from public databases. From this, we identified viral sequences belonging to thirty-six different viruses, of which twenty-two were classified as 'novel' as they exhibited less than 90 per cent amino acid identity to known viruses in the RNA-dependent RNA polymerase. Most of these novel viruses possessed genome structures similar to their closest relatives, with specific alterations in some cases. Phylogenetic analyses revealed that these viruses belonged to at least twenty-two viral families or unclassified groups, some of which were highly divergent from known taxa. Although further analysis failed to find venom-specific viruses, some viruses seemingly had much higher abundance in the venom-related microenvironment than in other tissues. In sum, our study provides insights into the RNA virome of the venom-related microenvironment from diverse animal phyla.

Evaluation of Antimicrobial Activity of Alocasia Cordfolia Rhizomes Extract

Objective: Discovering new antibacterial drugs with high efficacy and low toxicity from medicinal plants has received increasing attention worldwide. The aim of this study was to investigate the antimicrobial activity of ethanolic extract of Alocasia cordfolia rhizomes (ACRE). Methods: S.aureus, E.coli and C.albicans were selected as the tested microorganisms. The diameter of the inhibition zone was determined by the disc diffusion method, and MIC and MBC were measured using the broth microdilution method. Results: The diameter of the inhibition zone, MIC and MBC values of ACRE against S. aureus were 7.67±0.58 mm, 160 μg/μL and 320 μg/μL, and that of ACRE against C.albicans were 8.33±1.15 mm, 80 μg/μL and 160 μg/μL, respectively. However, ACRE did not show antimicrobial activity against E. coli. Conclusion: ACRE may be a potentially promising natural antimicrobial product, and further studies are needed to identify the specific active compounds present in this extract and to elucidate their antimicrobial mechanisms.

In Vitro and In Silico Studies of Antimicrobial Saponins: A Review

Antibiotics are important drugs for the treatment of microbial infections and related diseases. However, due to the abuse of antibiotics, drug resistance has become a serious and urgent problem. The development of new antibiotics is a crucial area of research, and natural products are one of the main sources of novel antibiotics. Among various potential natural antimicrobial products, saponins attracted much attention due to their excellent and broad-spectrum antimicrobial properties. Although there are several reviews on antibacterial saponins, this review is the first to highlight the potential antibacterial mechanisms of saponins from both experimental and molecular simulation perspectives to provide a comprehensive panorama of the field. This review presents the current progress in the development and repurposing of natural-product antibiotics. The focus is centered on antimicrobial saponins discovered in recent years as well as the synergistic effect of some saponins with traditional antibiotics. This review presents experimental and simulation studies in this field to provide a multiscale overview of the antimicrobial mechanisms of saponins and potential directions for future research.

Screening Amazon rainforest plant extracts for antimicrobial activity: a 15-year commitment to the Brazilian biodiversity

IntroductionThe need for new tools to treat infections is constantly growing due to the possibilities of emerging diseases related to environmental changes, climatic catastrophes, microorganism resistance, and human and animal aging, leading to an evident unbalance in the planet’s health. Brazil contains the most significant portion of world biodiversity, a potential source of new antimicrobial natural products. Nonetheless, its environment, particularly its forests, and rainforests, is under threat, meaning that rapidly conducted, comprehensive research into the potential of antimicrobial activity to address this threat is urgently needed.MethodsIn this study, plants from the Amazon rainforest and the Atlantic forests were collected and tested against several pathogenic microbes relevant to humans, animals, and the environment, and subjected to large-scale susceptibility assays, bioautography, and Artemia salina toxicity assays. From the plants, 2,280 organic and aqueous extracts were obtained from different organs, namely leaves, barks, flowers, fruits, and seeds, and subjected to a large-scale susceptibility screening assay against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus mutans, Streptococcus sanguinis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Malassezia pachydermatis, Malassezia furfur, and Listeria monocytogenes. Results and discussionThe selected extracts were subjected to antimicrobial susceptibility tests to determine their inhibition zone diameters and minimum bactericidal concentrations, to bioautography, and to an Artemia salina toxicity assay, which resulted in 154 active extracts. Moreover, 111 out of 154 extracts were ranked based on scores established by the p-values and the mean rank differences in each set of test results. The final ranking identified which extracts should be studied in further phytochemical research using thin-layer chromatography techniques as a priority. The extracts obtained from plants belonging to Combretaceae, Connaraceae, Convolvulaceae, Fabaceae, Malpighiaceae, Moraceae, Piperaceae, Polygonaceae, and Salicaceae were selected as the most promising ones and used to support the identification of plant-based antimicrobial active compounds from the immense biodiversity of Brazilian forests.

Enhancing the Production of Xenocoumacin 1 in Xenorhabdus nematophila CB6 by a Combinatorial Engineering Strategy.

Xenocoumacin 1 (Xcn1) is an excellent antimicrobial natural product against Phytophthora capsici. However, the commercial development of Xcn1 is hindered by the low yield, which results in high application costs. In this study, multiple metabolic strategies, including blocking the degradation pathway, promoter engineering, and deletion of competing biosynthetic gene clusters, were employed to improve the production of Xcn1, which was increased from 0.07 to 0.91 g/L. The formation of Xcn1 reached 1.94 g/L in the TB medium with the final strain T3 in a shake flask and further reached 3.52 g/L in a 5 L bioreactor, which is the highest yield ever reported. The engineered strain provides a valuable platform for production of Xcn1, and the possible commercial development of the biofungicide. We anticipate that the metabolic engineering strategies utilized in this study and the constructed constitutive promoter library can be widely applied to other bacteria of the genera Xenorhabdus and Photorhabdus.

Screen for New Antimicrobial Natural Products from the NCI Program for Natural Product Discovery Prefractionated Extract Library.

The continuing emergence of antibiotic-resistant microbes highlights the need for the identification of new chemotypes with antimicrobial activity. One of the most prolific sources of antimicrobial molecules has been the systematic screening of natural product samples. The National Institute of Allergy and Infectious Diseases and the National Cancer Institute here report a large screen of 326,656 partially purified natural product fractions against a panel of four microbial pathogens, resulting in the identification of >3000 fractions with antifungal and/or antibacterial activity. A small sample of these active fractions was further purified and the chemical structures responsible for the antimicrobial activity were elucidated. The proof-of-concept study identified many different chemotypes, several of which have not previously been reported to have antimicrobial activity. The results show that there remain many unidentified antibiotic compounds from nature.

Antimicrobial activity and chemical profile of wood vinegar from eucalyptus (Eucalyptus urophylla x Eucalyptusgrandis -clone I144) and bamboo (Bambusa vulgaris).

Microbial resistance to drugs is a public health problem; therefore, there is a search for alternatives to replace conventional products with natural agents. One of the potential antimicrobial agents is wood vinegar derived from the carbonization of lignocellulosic raw materials. The objectives of the present work were to evaluate the antibacterial and antifungal action of two kinds of wood vinegar (WV), one of Eucalyptus urograndis wood and another of Bambusa vulgaris biomass, and determine their chemical profile. The antimicrobial effect was assessed against Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enteritidis, Escherichia coli, Streptococcus agalactiae, and Candida albicans. The minimum inhibitory concentration and the minimum bactericidal and fungicidal concentrations were determined. Micrographs of the microorganisms before and after exposure to both kinds of wood vinegar were obtained by scanning electron microscopy. The chemical profile of the eucalyptus and bamboo vinegar was carried out by gas chromatography and mass spectrometry (GC/MS). Both types of WV presented significant antimicrobial activity, with the bamboo one having a higher efficiency. Both studied pyroligneous extracts seem promising for developing natural antimicrobials due to their efficiency against pathogens. GC/MS analyses demonstrated that the chemical profiles of both kinds of WV were similar but with some significant differences. The major component of the eucalyptus vinegar was furfural (17.2%), while the bamboo WV was phenol (15.3%). Several compounds in both WVs have proven antimicrobial activity, such as acetic acid, furfural, phenol, cresols, guaiacol, and xylenols. Together, they are the major in the chemical composition of the organic fraction of both WVs. Bamboo vinegar had a more expressive content of organic acids. Micrographs of microorganisms taken after exposure to both kinds of wood vinegar displayed several cell modifications. The potential of both types of wood vinegar as a basis for natural antimicrobial products seems feasible due to their proven effect on inhibiting the microorganisms' growth assessed in this experiment.

Essential Oils Infused Poly-ε-Caprolactone/Gelatin Electrospun Nanofibrous Mats: Biocompatibility and Antibacterial Study.

Infections caused by antibiotic-resistant pathogens result in a delayed wound-healing process. As an approach to prevent infections, alternatives in the form of natural antimicrobial products have become public interest. Essential oils derived from plants are used as antimicrobials owing to their broad-spectrum activity against pathogenic organisms. In this study, essential oil from seeds of watermelon, jackfruit, and papaya was incorporated into poly-ε-caprolactone/gelatin nanofibers using an electrospinning technique. The synthesized nanofibers were smooth, continuous, and bead-free. The nanofibers were found to be mechanically competent as confirmed by the universal tensile tester. The antibacterial activity of the various essential oil-loaded nanofibrous mats was determined by disc diffusion assay. Furthermore, they were found to be non-toxic and biocompatible by MTT and CMFDA assays on fibroblast cells. The obtained results have demonstrated that essential oil-loaded nanofiber mats are promising alternatives to conventional antibacterial wound dressings.

Improvement of chlorination and sterilization of pathogenic bacteria by natural products

There are many highly resistant pathogenic bacteria in the environment that cannot be removed by conventional chlorination disinfection. This study demonstrated a combined sterilization strategy for combating the extension of pathogenic bacteria by enhancing the bactericidal ability of sodium hypochlorite at subinhibitory concentrations with the utilization of the natural antimicrobial molecule cinnamaldehyde. The results indicated that treatment of cinnamaldehyde enhances the effect of chlorination disinfection, leading to an increase in concentration-dependent inactivation efficiency from 33.5 to 86.1%. Our results also proved that the combined sterilization strategy showed an inhibitory and destructive effect on the hazardous biofilm formed by Pseudomonas aeruginosa. Additionally, the cell membrane permeability and reactive oxygen species (ROS) levels were 1.8-fold and 2.3-fold increased compared with the controls, respectively, which revealed the synergistic effect and hypothetical mechanisms of natural antimicrobial products treatment to chlorination disinfection. This study provides further research for the control of drug-resistant bacteria in water treatment systems and contributes to combating the growing threat of antibiotic resistance.

Fusarium-Derived Secondary Metabolites with Antimicrobial Effects.

Fungal microbes are important in the creation of new drugs, given their unique genetic and metabolic diversity. As one of the most commonly found fungi in nature, Fusarium spp. has been well regarded as a prolific source of secondary metabolites (SMs) with diverse chemical structures and a broad spectrum of biological properties. However, little information is available concerning their derived SMs with antimicrobial effects. By extensive literature search and data analysis, as many as 185 antimicrobial natural products as SMs had been discovered from Fusarium strains by the end of 2022. This review first provides a comprehensive analysis of these substances in terms of various antimicrobial effects, including antibacterial, antifungal, antiviral, and antiparasitic. Future prospects for the efficient discovery of new bioactive SMs from Fusarium strains are also proposed.

Vaginal Sheets with Thymbra capitata Essential Oil for the Treatment of Bacterial Vaginosis: Design, Characterization and In Vitro Evaluation of Efficacy and Safety.

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with unpleasant odour. Excipients were selected to promote the healthy vaginal environment reestablishment and bioadhesion of formulations, while the TCEO acts directly on BV pathogens. We characterized vaginal sheets with TCEO in regard to technological characterization, predictable in vivo performance, in vitro efficacy and safety. Vaginal sheet D.O (acid lactic buffer, gelatine, glycerine, chitosan coated with TCEO 1% w/w) presented a higher buffer capacity and ability to absorb vaginal fluid simulant (VFS) among all vaginal sheets with EO, showing one of the most promising bioadhesive profiles, an excellent flexibility and structure that allow it to be easily rolled for application. Vaginal sheet D.O with 0.32 µL/mL TCEO was able to significantly reduce the bacterial load of all in vitro tested Gardnerella species. Although vaginal sheet D.O presented toxicity at some concentrations, this product was developed for a short time period of treatment, so this toxicity can probably be limited or even reversed when the treatment ends.

Antimicrobial Activity of Bioactive Compounds Isolated from Plant Endophytes

Abstract: To combat the escalating antimicrobial resistance, we need to develop new medications constantly. Recently, scientists more focused on endophytes to search for novel antimicrobial natural products. Endophytes are explored as 'bio-factories' of natural bioactive therapeutic compounds. These are microbes exhibited in plant living tissues without causing any harmful effect.Many therapeutic compounds isolated from endophytes are produced from biosynthetic pathways and belong to various structural groups like terpenoids, steroids, quinines, and phenols. Therapeutic compounds produced by endophytes exhibit different pharmacological properties. Fungal genera more commonly reside to plant tissue as compared to bacterial genera. The current review emphasizes comprehensive data on the antibacterial and antifungal activity and bio-therapeutic compounds produced by fungal and bacterial endophytes of some medicinal plants.

Identification and Analysis of Antimicrobial Activities from a Model Moss Ceratodon purpureus.

The emergence of bacterial drug resistance is often viewed as the next great health crisis of our time. While more antimicrobial agents are urgently needed, very few new antibiotics are currently in the production pipeline. Here, we aim to identify and characterize novel antimicrobial natural products from a model dioicous moss, Ceratodon purpureus. We collected secreted moss exudate fractions from two C. purpureus strains, male R40 and female GG1. Exudates from the female C. purpureus strain GG1 did not exhibit inhibitory activity against any tested bacteria. However, exudates from the male moss strain R40 exhibited strong inhibitory properties against several species of Gram-positive bacteria, including Staphylococcus aureus and Enterococcus faecium, though they did not inhibit the growth of Gram-negative bacteria. Antibacterial activity levels in C. purpureus R40 exudates significantly increased over four weeks of moss cultivation in liquid culture. Size fractionation experiments indicated that the secreted bioactive compounds have a relatively low molecular weight of less than 1 kDa. Additionally, the R40 exudate compounds are thermostable and not sensitive to proteinase K treatment. Overall, our results suggest that the bioactive compounds present in C. purpureus R40 exudates can potentially add new options for treating infections caused by antibiotic-resistant Gram-positive bacteria.

Bioassay-Guided Isolation of Antimicrobial Components and LC/QToF Profile of Plumeria obtusa: Potential for the Treatment of Antimicrobial Resistance.

The methanolic fraction (M-F) of the total extract (TE) of Plumeria obtusa L. aerial parts showed promising antibacterial effects against the MDR (multidrug-resistant) gram-negative pathogens Klebsiella pneumoniae and Escherichia coli O157:H7 [Shiga toxin-producing E. coli (STEC)]. In addition, M-F had a synergistic effect (in combination with vancomycin) against the MDR gram-positive strains MRSA (methicillin-resistant Staphylococcus aureus) and Bacillus cereus. After treating the K. pneumoniae- and STEC-infected mice with M-F (25 mg/kg, i.p.), the level of IgM and TNF-α was decreased and the severity of pathological lesions were reduced better than that observed after administration of gentamycin (33 mg/kg, i.p.). Thirty-seven compounds including 10 plumeria-type iridoids and 18 phenolics, 7 quinoline derivatives, 1 amino acid, and 1 fatty acid were identified in TE using LC/ESI-QToF. Furthermore, five compounds; kaempferol 3-O-rutinoside (M1), quercetin 3-O-rutinoside (M2), glochiflavanoside B (M3), plumieride (M4), and 13-O-caffeoylplumieride (M5) were isolated from M-F. M5 was active against K. pneumoniae (MIC of 64 μg/mL) and STEC (MIC of 32 μg/mL). These findings suggested that M-F and M5 are promising antimicrobial natural products for combating MDR K. pneumoniae and STEC nosocomial infections.