CPS is the most important virulence

factor of K. pneumoniae, which plays important

roles in resistance to phagocytosis, suppression of
early inflammatory response, resistance to antimicrobial
peptides, and inhibition of DC cell
maturation. Additional K. pneumoniae virulence
factors include LPS, fimbriae, outer membrane
proteins, and determinants for iron acquisition
and nitrogen source utilization.

Kapsul polisakarida merupakan faktor virulensi terpenting dari Klebsiella pneumoniae(Li et al., 2014)

Adanya kapsul yang tebal pada permukaan sel mampu melindungi Klebsiella pneumoniae dari

opsonisasi dan fagositosis oleh makrofag (Cortes et al., 2002), netrofil (Pan et al., 2011),

sel epitel (Sahly et al., 2000), dan sel dendrit (Evrard et al., 2010).

RESISTEN FAGOSITOSIS

Adanya…… K1 Klebsiella pneumoniae yang hipervirulen mudah menghindari reaksi neutrofil intraseluler dan
memindahkan K1 menuju organ lain, seperti hati, yang pada akhirnya akan menyebabkan abses. Selain itu,
dibandingkan dengan strain yang nonhipervirulen, K1 pada Klebsiella pneumoniae yang hipervirulen menunjukkan
level interaksi lebih rendah terhadap makrofag (Wu (Chang et al., 2008). Hal ini disebabkan oleh adanya substansi
piruvat luas pada asam glukoronik dan asetilasi C2-OH atau C3-OH pada fucose dalam kapsul polisakarida K1(Yang
et al., 2011).

Chang, 2008

Yang 2011

Campos 2004

Llobet 2008

Evrard 2010

RESISTEN ANTIMIKROBIAL PEPTIDES

Permukaan sel kapsul polisakarida pada Klebsiella pneumoniae memiliki aksi protektif terhadap efek peptide
antimikroba inang. Kapsul polisakarida yang bebas dapat menangkap polipeptida antimikroba sehingga
dapat mengurangi jumlah polipeptida antimikroba yang menjangkau permukaan bakteri(Campos et al.,
2004). Selain itu, konsentrasi subletal pada peptide antimikroba dapat menginduksi ekspresi gen,
sehingga dapat melindungi bakteri dari aksi polipeptida. (Llobet et al., 2008).

INHIBISI MATURASI DC

K. pneumoniae CPS can impair DC maturation

(Figure 1) andthereby reduce the DC-mediated
production of pro-Th1 cytokines, such as IL-12
and TNF-α, which will lead to the destructive
function of immature DCs during K. pneumoniae
antigen presentation (thereby impairing
T-cell activation), and moreover result in
reduced DC-mediated natural killer cell migration
[29]. Taken together, inhibition of DC
maturation by K. pneumoniae CPS allows the
bacteria to avoid the host defenses and thus to
multiply in vivo more easily.

Kapsul polisakarida pada Klebsiella pneumonia dapat mengganggu proses maturasi sel dendrit. Hal ini
menyebabkan penurunan produksi sitokin pro-Th1oleh sel dendritik (seperti IL-12 dan TNF-α , yang kemudian akan
merusak fungsi sel dendritik selama Klebsiella pneumoniae mengeluarkan antigen, sehingga mengganggu aktivasi
sel T) dan akhirnya mengurangi migrasi sel natural killer (Evrard, 2010). Bersama-sama, penghambatan maturasi
sel dendritik oleh kapsul polisakarida Klebsiella pneumoniae menyebabkan bakteri mudah menghindari pertahanan
inang sehingga dapat dengan mudah berkembang secara in vivo.

The lamina of leaf is smooth with even surface (Figure 3a). It has thickness of 160-170μm with adaxial
epidermis of 20μm thickness and abaxial epidermis of 12 μm thickness with short cylindrical finger like
glandular trichomes (pearl glands). These glandular trichomes are 30μm long and 5μm thick (Figure 3b).
The
abaxial epidermis is stomateferous while adaxial epidermis is apostomatic. The stomata are cyclocytic
type
(Figure 4a,4b). They have single row of short, wide vertically oblong palisade cells and spongy
mesophyll of 3
or 4 layers with secretory cells of 25-30 μm in diameter (Figure 5). The petiole is roughly triangular and
outline
has deep furrows and ridges. Inner part of the ridges is collenchymatous (Figure 6). SEM showed
pearlglands,
cyclocytic stomata in lower epidermis of leaf and subsidiary cells (Figure 7a,7b). The petiole showed
numerous
covering trichomes (Figure 7c).

Lamina pada daun sirih bertekstur lembut, termasuk pada bagian permukaan. Ketebalannya sekitar 160-
170µm dengan serat trikoma berbentuk silinder menjari. Panjang serat trikomanya kurang lebih 30µm
dengan tebal sekitar 5µm. Stomata daun sirih memiliki tipe cyclocytic.

The bioactive molecule

thought to be responsible for anti-bacterial
activity is sterol, which has been obtained in large
quantities in betel leaf extracts. The mode of
action may be due to surface interaction of sterol
molecule present in the extracts with the bacterial
cell wall and membrane leading to alteration in
the primary structure of cell wall, ultimately lead
to pore formation and degradation of the bacterial
components. It is reported that sterol act through
the disruption of the permeability barrier of
microbial membrane structures[

Molekul bioaktif pada tanaman sirih yang diyakini berperan penting dalam efek antibakterial adalah sterol. Molekul sterol mampu
berinteraksi dengan dinding sel dan membran sel bakteri yang menyebabkan perubahan struktur primer dinding sel. Hal ini
menyebabkan degradasi komponen bakteri. Sterol juga mempu merusak barier permeabilitas pada struktur membran mikroba.

Allylpyrocatechol (APC) an allyl-substituted catechol is the

major phenolic constituent responsible for the
antioxidant properties in ethanolic of P.betle extracts 24,25.
Moreover, compounds such as polyphenol like eugenol,
chavicol, chavibetol and carvacrol are other active
components in P.betle extracts are responsible to upregulate
its antioxidant effect 26. Ethanolic extract
demonstrated significant direct killing ability of S.aureus.
The mechanism by which the extract exerts this effect is
unknown although it is suggested that presence of
ethanol in extract has antimicrobial effects on S.aureus by
damaging its cell membranes 27. However, a similar study
using the killing assay showed that the growth of bacteria
declined after treatment with P.betle extract, suggesting
effective killing potential ofS.aureus28.

Komponen polifenol seperti eugenol, chavicol, chavibetol