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Herbal Extracts with Anti-MRSA and Quorum Sensor
Neutralization Activities
HUSSEIN El Haj Ahmad
SUNIL Maharjan
RATISH S. Pillai
MRSA causes infections:
• In hospitals including:– Catheter-associated bacteraemia– Surgical site infections– Ventillator-associated pneumonia (VAP)
• In community– patients who lack traditional MRSA risk
factors
Alp and Voss (2006); HPA (2007); CDC (2007).
High Global MRSA Prevalence
Canada 2.3%
USA 55%
UK 44%
Australia 26%
China 39%
Japan 74%
Hong Kong 80%
Singapore 63%
South Africa 49%Nigeria 21%
Latin America 29%
Germany 25%France 27%Spain 27%Romania 61%Cyprus 56%
Netherlands 1%
Alpesh and Batts (2006); EARSS (2005); PHAC (1997); Collignon et al (2005).
4
9
22
40
33
30
2
4342
44
39
44
0
5
10
15
20
25
30
35
40
45
50
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Years
% M
RSA
in I
nfec
tions
Dia
gnos
ed fo
r St
aphy
loco
ccus
aur
eus
HPAEARSS
MRSA Prevalence in UK Between 1990 and 2005
HPA (2007); EARSS (2005).
20.6
32.547.2
60.6 70.4
68.1
72
78.2
11.8
58.2
40.3
49.650.5
0
10
20
30
40
50
60
70
80
90
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Years
% M
RS
A in
Dea
ths
Dia
gnos
ed f
or
Sta
phyl
ococ
cus
aure
us
NS
MRSA Deaths in UK
National Statistics online (February 2007).
This increase may be related to improved levels of reporting on death certificates.
MRSA Resistance
• MSRA is resistant to several classes of antibiotics.
• Emerging problem: formation of tolerant biofilm – causing chronic and recurrent nosocomial device-related
infections
• Increased demand for new anti-infectives and novel strategies to control MRSA infections
Alpesh and Batts (2006); Rice (2006); Costerton et al., (1999); Donlan and Costerton (2002); Lewis (2001).
– Downregulation of microbial virulence factors– Inhibition of biofilm formation
• Those agents are known as QSI.
• Crude extract and toluene extract of garlic showed– QSI activity against Pseudomonas aeruginosa– Synergism with some conventional antibiotics at sublethal
concentration
• Until now garlic extract and allicin activities against MRSA biofilms are not studied.
Antipathogenic Agents
Watnick and Kotler (1999); Davies et al. (1998); Rasmussen (2005).
MRSA Market
• MRSA market of five antibiotics had increased from 570 million USD in 2002 to 1.5 billion USD in 2006.
• To have a share in this growing market, some pharmaceutical companies are developing newer anti-MRSA agents in their pipelines. – Arpida (iclaprim)– GlaxoSmithKline (pleuromitilin)– Astra-Zeneca (AZD1279)
• Why not to have a share in this market?
Aim
This research aims to study whether:
Allicin alone, allicin mixed with toluene, toluene-, ethanol-, and chloroform- extracts of garlic can prevent or not MRSA biofilm formation.
Materials and Methods
• Clinical isolates– Clinical MRSA isolates, MRSA control strain,
Pseudomonas aeruginosa positive control strain.
• Chemicals– Aqueous extract of allicin, allicin + toluene,
toleuene extract of garlic, ethanol-extract of garlic, and chloroform-extract of garlic.
• MIC and MBC– MIC & MBC of planktonic bacteria and those in
biofilms will be determined according to BSAC guidelines.
Materials and Methods
• Biofilm formation– Plasma method– MBECTM-HTP Assay in Calgary Biofilm Device
• Measurement of microbial count, viability and killing in MRSA biofilms– Microbial viable count will be determined on real-
time basis by plate count and luminometry.
Summary• Global increase in MRSA prevalence
• MRSA grows in biofilms thus increasing its resistance
• Any agent interfering with QS will inhibit biofilm formation and decrease microbial pathogenicity.
• If allicin inhibits MRSA biofilm formation:– it may act as QSI– proven antimicrobial activity, promising natural
agent against serious MRSA infections.
THANK U