Antimicrobial Potential of Allium sativum in the Era of Antibiotic Resistance: Gaps and Future Perspectives

Jefferson Lorenconi de Morais¹*, Larissa Neres Barbosa², Lanna Araújo Gomes².

1*Polytechnic School of the Alves Faria University Center, UNIALFA, Brazil.

2 Department of Pharmaceutical Sciences and Chemistry, University Center of Goiás, UNIGOIÁS Brazil.  

*Correspondence: jefferson.morais@unialfa.com.br

 DOI: https://doi.org/10.71431/IJRPAS.2026.5402

 INTRODUCTION

Antimicrobial resistance (AMR) represents one of the greatest global public health challenges of the 21st century, compromising the efficacy of conventional therapies and significantly increasing morbidity and mortality associated with bacterial infections [1]. The rising prevalence of multidrug-resistant (MDR) microorganisms, such as Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, underscores the urgent need for novel therapeutic strategies [2].

In parallel, there is growing interest in the use of natural compounds with antimicrobial properties, particularly those derived from medicinal plants. Among these, garlic (Allium sativum) stands out as one of the most promising phytotherapeutic agents, having been widely used in both food and traditional medicine for millennia [3,4]. Historical evidence indicates that garlic was employed by ancient civilizations, including Egyptians, Greeks, Chinese, and Indians, for the treatment of infections and various ailments [5].

The origin of garlic dates back to Central Asia, with records of use exceeding 5,000 years, having spread globally through trade routes and cultural exchange [16,17]. Throughout history, its application transcended culinary use, being employed as a therapeutic agent in contexts such as epidemics, warfare, and traditional medical practices [2,5]. During periods such as the Middle Ages and up to the Second World War, garlic was used as an antimicrobial alternative in the absence of modern antibiotics [2].

From a molecular standpoint, the biological effects of garlic are primarily attributed to organosulfur compounds, including allicin, ajoene, diallyl disulfide (DADS), and diallyl trisulfide (DATS) [6,7]. These compounds are formed from the conversion of alliin by the enzyme alliinase when garlic tissue is disrupted, resulting in highly reactive and biologically active metabolites [8]. Allicin, in particular, exhibits potent antimicrobial activity due to its capacity to interact with sulfhydryl (–SH) groups of bacterial enzymes, thereby impairing essential metabolic functions [1,8].

Beyond bactericidal activity, recent studies demonstrate that garlic compounds possess antibiofilm, antivirulence, and quorum sensing inhibition properties — mechanisms fundamentally associated with bacterial resistance [1,8]. These multiple pathways of action render garlic a relevant candidate in the development of alternative or complementary therapies to conventional antibiotics. However, despite its potential, several challenges still limit clinical application, including chemical variability, low stability of active compounds, pharmacokinetic limitations, and lack of standardization in formulations [7]. Furthermore, the majority of studies remain focused on in vitro models, with a scarcity of robust clinical evidence [8].

Given this scenario, a critical analysis of the current state of knowledge on the use of garlic in combating bacterial resistance is essential to identify scientific gaps and future perspectives for its therapeutic application.

Molecular Properties and Bioactive Compounds of Allium sativum

The therapeutic potential of Allium sativum is directly related to its complex chemical composition, characterized primarily by the presence of biologically active organosulfur compounds. These compounds are responsible for the majority of the pharmacological effects of garlic, including its antimicrobial, antioxidant, and anti-inflammatory properties [1,7].

Precursor Compounds and Allicin Formation

In its intact state, garlic predominantly presents stable sulfur compounds, such as alliin (S-allyl-L-cysteine sulfoxide), stored in the cytoplasm of plant cells [1]. When garlic tissue is damaged by cutting or crushing, the enzyme alliinase is released, catalyzing the conversion of alliin into allicin (diallyl thiosulfinate), a highly reactive and unstable compound [1,7]. Allicin is considered the principal bioactive agent of fresh garlic, being responsible for its characteristic odor and for a large portion of the antimicrobial activity observed in experimental studies. Due to its chemical instability, allicin rapidly decomposes into other secondary sulfur compounds, including DADS, DATS, ajoene, and vinyldithiins. These metabolites exhibit greater stability and contribute significantly to the biological effects of garlic [1,7].

Classes of Bioactive Compounds

The bioactive compounds of garlic can be classified into three principal groups:

Fat-soluble compounds (garlic oil) include diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), obtained primarily by distillation or thermal processing. They exhibit high antimicrobial activity, especially against both Gram-positive and Gram-negative bacteria [1]. Water-soluble compounds include S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC). These compounds are more stable and exhibit greater bioavailability, being frequently found in aged garlic extract (AGE) [7]. Intermediate compounds (thiosulfinates), principally allicin, possess high chemical reactivity and are considered the primary agents responsible for the immediate antimicrobial activity of fresh garlic [1].

Figure 1. Molecular properties of Allium sativum and ROS-mediated antimicrobial mechanisms. Left panel: key organosulfur compounds (allicin, ajoene, DADS, DATS). Right panel: ROS-induced bactericidal effects including membrane peroxidation, enzyme/protein damage, DNA disruption, and biofilm degradation [1,8].

Molecular Mechanisms of Antimicrobial Action

The organosulfur compounds of garlic act through multiple mechanisms, which reduces the likelihood of bacterial resistance development [1,7,8]. Allicin reacts with thiol groups present in essential bacterial enzymes, leading to inhibition of critical metabolic processes such as protein synthesis and energy production [1,8]. Fat-soluble compounds such as DADS and DATS induce alterations in bacterial membrane permeability, resulting in cellular lysis [8]. Furthermore, garlic interferes with bacterial quorum sensing, reducing the expression of virulence-related genes and biofilm formation [1,8]. The ability to prevent biofilm formation and promote degradation of pre-formed biofilms represents a significant advantage over traditional antibiotics [8]. Studies also indicate that garlic compounds can alter bacterial gene expression and interfere with critical metabolic pathways [2].

Molecular and Pharmacological Limitations

Despite the great therapeutic potential of Allium sativum, several limitations related to its molecular properties hinder clinical application: instability of allicin, whereby rapid degradation reduces in vivo efficacy [7]; low standardization due to variations in chemical composition depending on processing conditions [7]; variable bioavailability among formulations (oil, extract, powder) [7]; and interactions with biological proteins, leading to reduced activity in thiol-rich environments such as the human body [1]. These limitations reinforce the need for development of novel strategies, such as controlled-release systems and nanoencapsulation, aimed at increasing stability and efficacy of garlic bioactive compounds [7].

OBJECTIVES

The present study aims to conduct a systematic review of the literature, based on PRISMA guidelines, on the potential of Allium sativum as an antimicrobial agent against resistant bacteria, with emphasis on the analysis of its bioactive compounds, mechanisms of action, current limitations, and perspectives for clinical application.

JUSTIFICATION

The increasing bacterial resistance and the scarcity of new effective antibiotics demand the investigation of innovative therapeutic alternatives. Garlic, presenting multiple mechanisms of antimicrobial action and a well-established history of medicinal use, emerges as a promising option. However, the absence of methodological standardization and the gap between experimental evidence and clinical application justify the need for systematic reviews that consolidate existing knowledge and guide future research [2,7].

MATERIALS AND METHODS

Study Design

This study is characterized as a systematic literature review, conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to ensure transparency, reproducibility, and methodological rigor in the selection and analysis of included studies.

Search Strategy

The bibliographic search was conducted across recognized scientific databases, including PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar (as a complementary source). Controlled descriptors (MeSH) and free terms combined with Boolean operators (AND, OR) were employed, as follows:

("Allium sativum" OR garlic) AND (antibacterial OR antimicrobial OR "antimicrobial activity") AND ("antibiotic resistance" OR "multidrug resistance" OR MDR OR AMR) AND (phytotherapy OR "natural compounds" OR "plant extract")

Inclusion and Exclusion Criteria

Inclusion criteria: original articles and reviews published in peer-reviewed journals; studies addressing the antimicrobial activity of Allium sativum; studies related to bacterial resistance (AMR or MDR); in vitro, in vivo, or clinical studies; publications in English, Portuguese, or Spanish; publication period from 2000 to 2025.

Exclusion criteria: duplicate studies; studies without access to full text; articles not directly addressing the antimicrobial activity of garlic; studies focused exclusively on other plants; studies with poor methodological quality or lacking scientific rigor.

Study Selection Process

The selection process was conducted in four stages: (1) identification — articles identified in databases according to the defined search strategies; (2) screening — removal of duplicate articles, followed by title and abstract reading for relevance verification; (3) eligibility — full-text reading of potentially relevant articles; and (4) inclusion — final selection of studies meeting all established criteria for qualitative analysis and discussion.

PRISMA Flow

Records identified in databases (PubMed, Scopus, Web of Science, ScienceDirect): n = 640. Records after duplicate removal: n = 460. Records excluded at initial screening: n = 300. Full-text articles assessed for eligibility: n = 160. Articles excluded after full-text reading: n = 110. Studies included in the final review: n = 50.

Figure 2. PRISMA 2020 flowchart of the study selection process. Records identified through database searching (n = 640), after duplicate removal (n = 460), full-text articles assessed (n = 160), and studies included in the final systematic review (n = 50).

5.6 Data Extraction and Analysis

The following information was extracted from each selected study: author and year of publication; type of study (in vitro, in vivo, clinical); type of garlic extract or compound used; microorganisms tested; principal results (antimicrobial activity, MIC values); proposed mechanisms of action; and study limitations. Analysis was conducted in a qualitative and comparative manner, seeking to identify patterns, gaps, and future perspectives in the use of garlic as an antimicrobial agent.

RESULTS AND DISCUSSION

General Characterization of Included Studies

Analysis of the 50 selected studies revealed that the majority of research on Allium sativum focuses on in vitro assays, with a smaller proportion of in vivo studies and a scarcity of clinical trials. The included studies addressed different forms of garlic preparation, including aqueous extract, essential oil, ethanolic extract, and isolated compounds such as allicin and sulfur derivatives [1,7]. The most frequently investigated microorganisms included Gram-positive and Gram-negative bacteria, with particular attention to MDR strains: Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. These pathogens are widely recognized as priority organisms by the World Health Organization due to their elevated resistance to antibiotics [2].

Antimicrobial Activity Against Resistant Bacteria

The analyzed studies demonstrate that garlic exhibits significant antimicrobial activity against resistant strains, including MDR bacteria. Allicin and other organosulfur compounds proved effective in inhibiting bacterial growth, with minimum inhibitory concentration (MIC) values varying according to the type of extract and microorganism [1,8,13]. In addition to direct bactericidal activity, garlic demonstrated reduction of bacterial viability, inhibition of biofilm growth, and suppression of bacterial virulence [10,11]. These effects are particularly relevant given that bacterial biofilms represent one of the principal mechanisms of antimicrobial resistance [8].

Mechanisms of Action Against Bacterial Resistance

One of the principal distinguishing features of Allium sativum is its action through multiple simultaneous mechanisms, which reduces the probability of bacterial resistance development [1,7]. Allicin reacts with essential bacterial enzymes, compromising critical metabolic processes [1]. Fat-soluble compounds promote structural alterations to the bacterial membrane, resulting in cell lysis [8]. Garlic also interferes with bacterial communication, reducing the expression of virulence factors and preventing biofilm formation [1,8]. The ability to prevent formation and promote degradation of biofilms represents a significant advantage over traditional antibiotics [8].

Comparison with Conventional Antibiotics

Several studies indicate that garlic may act both as an isolated antimicrobial agent and as a potential therapeutic adjuvant. Garlic compounds can potentiate antibiotic action, reduce required drug dosages, and partially reverse resistance mechanisms [7,13]. These effects suggest that garlic may play a relevant role in strategies to combat bacterial resistance, especially in combined therapies [2].

LIMITATIONS OF CURRENT STUDIES

Despite the promising results, important limitations were identified in the reviewed literature: predominance of in vitro studies that do not adequately reflect real physiological conditions; variability in chemical composition due to differences in garlic processing [7]; rapid degradation of allicin limiting clinical application [7]; absence of uniform experimental protocols hindering cross-study comparisons; and a scarcity of robust clinical evidence in humans [8].

FUTURE PERSPECTIVES

The results indicate that garlic possesses high potential as an antimicrobial agent, especially in the context of growing bacterial resistance. Key future directions include: development of nanoformulations to increase stability [7]; standardization of extracts and active compounds; randomized clinical trials; investigation of combined therapies with antibiotics; and application in personalized medicine and precision pharmacology. Furthermore, approaches based on artificial intelligence and molecular modeling are being utilized to identify new therapeutic targets and optimize garlic-derived compounds [7].

CONCLUSION

The present systematic review demonstrated that Allium sativum possesses a broad spectrum of antimicrobial activity, including efficacy against multidrug-resistant (MDR) bacteria, positioning itself as a potential therapeutic agent in the era of antimicrobial resistance. Organosulfur compounds, especially allicin and its derivatives, demonstrated action through multiple mechanisms — including enzyme inhibition, cell membrane disruption, quorum sensing interference, and antibiofilm activity — which reduces the likelihood of bacterial resistance development [1,8].

The analyzed results indicate that garlic may act both as a direct antimicrobial agent and as a therapeutic adjuvant, potentiating the action of conventional antibiotics and contributing to strategies to combat bacterial resistance [2,7]. Nevertheless, the clinical application of garlic is still limited by factors such as the chemical instability of active compounds, variability in extract composition, low methodological standardization, and scarcity of robust clinical trials [7,8].

Although garlic presents high therapeutic potential, its translation from the experimental setting to clinical practice depends on the development of more sophisticated approaches, including controlled-release technologies, pharmaceutical standardization, and large-scale clinical validation [7].

SCIENTIFIC CONTRIBUTIONS

The present study contributes to scientific advancement by: (1) integrating evidence on the antimicrobial potential of garlic, providing a consolidated view of the efficacy of Allium sativum against resistant bacteria; (2) evidencing multiple mechanisms of action of organosulfur compounds, reinforcing the relevance of garlic as an agent capable of circumventing classical bacterial resistance mechanisms; (3) identifying relevant scientific gaps, including the predominance of in vitro studies, absence of standardization, and scarcity of clinical trials; (4) indicating the potential of garlic as a therapeutic adjuvant in association with antibiotics; and (5) indicating future perspectives for research and innovation, such as nanotechnology, molecular modeling, and precision pharmacology [1,7,8].

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

ACKNOWLEDGEMENTS

The authors would like to thank the academic and research institutions that supported this work.

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