Antibacterial Efficacy Of Allium Sativum Against Multidrug-Resistant

Bacterial Pathogens And Its Synergistic Interaction With Conventional

Antibiotics

Author Name: Mustafa Raheem Tuamah

Address: Iraq /Babylon/Al-Muhaweel/Al-Katonya village
Tel: 07812123306
E-mail: [email protected]
Place: DNA Research center, University of Babylon, Babylon, Hillah, 51001, Iraq

ABSTRACT

The global rise in antibiotic resistance poses a significant threat to public health,
primarily driven by the widespread and often indiscriminate use of antibiotics. This has led to
the emergence of multidrug-resistant (MDR) bacterial strains, diminishing the efficacy of
many conventional antimicrobial agents and contributing to increased morbidity and
mortality. In response to this growing crisis, the search for alternative and complementary
therapeutic strategies has intensified. Medicinal plants, particularly those used in traditional
medicine, have long been recognized for their therapeutic potential in treating various human
diseases. Among these, Allium sativum (garlic) is well-documented for its broad-spectrum
antimicrobial properties, low cost, and minimal side effects. Natural plant-derived
compounds offer a promising avenue for developing new antibacterial agents that are both
effective and safe.

KEYWORDS: multidrug-resistant, Allium sativum, antimicrobial properties, antibiotic

resistance

INTRODUCTION

The increasing mortality rate of infectious diseases is one the most challenging public
health problems faced by different countries worldwide (Tuyishime Gabriel. et al.; 2022).
Unfortunately, the wide use of antibiotics has increased the development of bacterial resistant
strains to antibiotics (Andersson, D.I.; Hughes, D. 2011), which has resulted in a reduction in
the effectiveness of some of the antibacterial agents, leading to high mortality rates.
Medicinal plants have been used for many years in the treatment of a vast number of human
diseases by the community, specifically in traditional medicine (Tuyishime Gabriel. et al.;
2022). They are considered the main source of new, natural, and safe drugs to be utilized
in managing diseases as an effective and harmless alternative medicine, because they are not
expensive and pose minimum side effects to humans (Singh B. et al.; 2020). According to a
report published in 2002 by the World Health Organization (WHO) in Geneva, medicinal
plants have significant value and could be considered as the best source of complementary
and alternative natural medicines (WHO. 2002). Garlic, scientifically known as Allium
sativum, is one of the oldest plants used as a spice in food and also used as a medicine
because of its many benefits to human health and wellbeing (Botas J. et al.; 2019). Results
from different studies have shown that garlic extracts have the capacity to inhibit the growth
of some pathogenic microorganisms (Chen C. et al.; 2018).

DEFINITION OF ANTIBIOTIC RESISTANCE

 Antimicrobial resistance poses a serious threat to global public health, causing at least
1.27 million deaths globally and approximately 5million fatalities in 2019 (Helal F. Hetta et
al.; 2023). More than 35,000 people die as a result, according to CDC’s 2019 Antibiotic
Resistance (AR) Threats Report (CDC. 2022). Antimicrobial resistance may have an
impact on individuals at every stage of life, as well as on the medical, veterinary, and
agricultural sectors (Nageeb W.M. et al.; 2022). This makes it one of the most important
public health issues in the entire world (CDC. 2022). Rapid development of Ab resistance in
microorganisms is directly related to overconsumption of Abs, their broad utilization in
agriculture (Ventola, C.L. et al.; 2015). Due to the fact that repeated drug administration and
greater doses are common nowadays, Antibiotic resistance has emerged against various types
of antibiotics commonly used against harmful bacteria (Teixeira M. et al.; 2018).

DEVELOPMENT OF BACTERIA ANTIBIOTIC RESISTANCE

Bacteria are living entities that change over time. Their major goal is to multiply,
endure, and spread as quickly as they can. Microbes, as a result, adapt to their environment
and develop in ways that ensure their survival (MacGowan, A. et al.; 2017, El-Mokhtar, M.A.
et al.; 2018). If anything, such as an antibiotic, inhibits their ability to develop, genetic
changes may occur, rendering the bacteria resistant to the medicine and enabling them to
survive (Munita, J.M. et al.; 2016, Helal F. Hetta et al.; 2023). Antibiotics can be rendered
inactive by bacteria via a variety of molecular mechanisms (Helal F. Hetta et al.; 2023)
Production of inactivating enzymes: The bacteria produces enzymes that inactivate the
antibiotic, causing it to lose its biological function (El-Kazzaz, W. et al.; 2020).
 Change and alterations in the antibiotic target (Algammal, A.M et al.; 2020).
 Decrease in antibiotic uptake : Change in the structure of cell surface casing can
reduce the entry of an antibiotic (Kareem, S.M. et al.; 2021).
 Extrusion of drug outside the cell: Energy-driven drug efflux systems eliminate
antibiotics that have been taken up by bacterium cells. (Abd El-Baky, R.M et al.;
2019).
 Activation of alternative metabolic pathways: Bacteria exposed to antibiotic are still
able to produce substances through a different metabolic pathway (Ovung, A. et al.;
2021).
 Transferring of resistance genes: As a result of bacterial communication and genetic
information sharing, resistance genes transfer among bacterial populations (Blair J. et
al.; 2015).
 Extracellular biofilm formation: Some antibiotics are unable to penetrate the
protective extracellular of bacterial biofilms (Khalil, M.A. et al.; 2021).
Once a species gains resistance to an antibiotic, it eventually overcomes the combined
drug effects, leading to development of multidrug-resistant (MDR) organisms which are
resistant to antimicrobial drugs or combination treatments. By encouraging bacterial growth
that was not immediately eliminated, this scenario occasionally encourages the spread of
resistance (Torky H.A. et al.; 2023, Mabrok M. et al.; 2023).

MULTI-DRUG RESISTANCE BACTERIA STRAINS

Increased antibiotic resistance is among the world’s top three public health issues of
the 21st century, according to the World Health Organization (WHO). The much more
harmful bacteria, collectively known as ESKAPE are those that cause the most concern:
 E. coli
 Staphylococcus
 Klebsiella
  Pseudomonas ,they are all are connected to a high death rate )Algammal A.M et al.;
2020).
S. aureus can cause:( Pimples, boils or other skin conditions, Bloodstream infections or sepsis
, Pneumonia, Endocarditis (infection of the heart valves), which can lead to heart failure and
Osteomyelitis (bone infection) (CDC. 2024). E. coli can make people sick with diarrhea,
urinary tract infections, pneumonia, sepsis, and other illnesses (CDC. 2024). Klebsiella can
cause pneumonia, bloodstream infections, wound or surgical site infections, and meningitis
(CDC. 2024). P. aeruginosa can cause infections in the burn, blood, lungs (pneumonia),
urinary tract or other parts of the body after surgery (CDC. 2024). The spread of MDR and
extensively drug-resistant (XDR) bacteria continues to represent a severe threat to human and
animal health due to their high mortality, morbidity, and prices of medication to combat them
)Algammal A.M et al.; 2021). This is made worse by a number of bacterial strains’ capacity
to form biofilms, which is linked to 65–80% of human illnesses (Lebeaux D. et al.; 2013).
MDR causes blockage in the fight against disease and decreases treatment effectiveness,
which causes the patient’s infection to last longer than expected (Helal F. Hetta et al.; 2023).
Immunocompromised patients such as those with chronic diseases, receiving cancer
chemotherapy, immunosuppressive drugs or undergo organ transplantation are more
vulnerable to MDR infection (Helal F. Hetta et al.; 2023). Additionally, the treatment cost has
also increased as a result of MDR since microorganisms have developed resistant to
commercially accessible Abs, necessitating the adoption of a more expensive one (Tanwar, J.
et al.; 2014).
Allium sativum (Garlic) as alternative treatment
In recent years, awareness of the issue of antibiotic resistance has increased, including
in the political field: In 2017, the countries decided to intensify global collaboration on this
issue to stimulate the R&D of antimicrobial molecules, also starting from existing antibiotics
(WHO. 2021). Since 2017, eight new antibiotics have been approved by the FDA, including
one for the treatment of multidrug-resistant tuberculosis: Most of these drugs were developed
from traditional molecules and target Enterobacteriaceae resistant to carbapenems and other
pathogens considered dangerous by WHO (WHO. 2021). Findings have shown that garlic can
be used in the management of various diseases such as cardiovascular disease and
hyperglycemia (Tuyishime Gabriel. et al.; 2022). Additionally garlic has been approved to
reduce the risk of cancer, boosting the immune system and protecting against inflammation as
well as infectious diseases (atiño-Morales C.C. et al.; 2022). Their antimicrobial activity has
been linked to the presence of sulphur compounds, specifically, allicin which is the
compound produced by the alliin lyase enzyme, after crushing or bruising a garlic bulb
(Bhatwalkar S.B. et al.; 2021). Many medical bacteria, including grampositive
and gram-negative strains, are sensitive to garlic extracts (Fufa B. 2019), indicating that
garlic has a reliable broad spectrum of activity related to its chemical composition (Sasi M. et
al.; 2021). However, the amounts and types of antimicrobial substances extracted depend on
diverse extraction methods (Tuyishime Gabriel. et al.; 2022). Allicin is a reactive sulfur
species and reacts with free thiol groups such as those in protein cysteine or glutathione; thus
it has a wide range of cellular targets (Jana Reiter et al.; 2020). GSH is oxidized by allicin to
S-allylmercaptoglutathione (GSSA), diminishing the cellular GSH pool and leading to
oxidative stress in the cell (Jana Reiter et al.; 2020). Furthermore, allicin oxidizes accessible
cysteine in proteins to produce Sallylmercapto- adducts (Jana Reiter et al.; 2020). S-
thioallylation of cysteine can inhibit essential enzymes, or disrupt signal transduction by
changing the three-dimensional conformation of proteins, or preventing metal cofactor
binding; these properties are generally thought to be responsible for allicin’s antimicrobial
activity (Jana Reiter et al.; 2020).
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