ResearchPaper

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Bacteremia:
An agr-Status Independent Infection
By: Samantha Lau

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Abstract:
Staphylococcus aureus is the cause of many hospital-acquired infections. When it
colonizes an individual, it is usually found on the skin, in the anterior nares or in the
bloodstream. It was hypothesized that the isolates in the bloodstream are of the same mutant as
those in the anterior nares. To test this hypothesis, cultures from both the blood and the anterior
nares of patients infected with Staphylococcus aureus bacteremia, and cultures from only the
anterior nares of patients that were not infected with Staphylococcus aureus were collected. The
agr-status, mutations and repeats of the cultures collected were determined by cross-streaking
colonies from diluted bacterial solutions, by extracting the DNA of the colonies, and by spa
typing them to sequence the DNA. In comparing the agr-status of the cultures from the anterior
nares and from the blood, it was found that the agr-status of the cultures were the same.
Furthermore, it was found that mutations and repeats of the cultures from the anterior nares and
from the blood were identical. Therefore, it was concluded that patients are colonized by
Staphylococcus aureus strains of one mutant, and that the hypothesis that cultures in the
bloodstream are derived from the isolates in the anterior nares was supported. It was also
concluded that the agr-status of the strain does not affect the probability of developing a
Staphylococcus aureus infection.

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Introduction:
The spread of bacterial infections, particularly that of Staphylococcus aureus infections,
has been a longstanding issue. Staphylococcus aureus is associated with many respiratory
infections. Between 1979 and 1995, it caused at least 13% of the hospital-acquired infections and
about 10% to 40% of the infections resulting from nasal carriage of the bacteria (von Eiff, 2001).
The infections caused by S. aureus range from infections as small as food poisoning, diarrhea
and dehydration to infections as large as toxic shock syndrome, pneumonia and scalded skin
syndrome (Lowy, 1998). Usually located on the skin and in the nose of 25% to 30% of healthy
individuals, S. aureus only causes a problem when it passes the skin barrier and is given access
within the body (Traber, 2008). To treat severe infections, antibiotics are given based on the S.
aureus strain’s likelihood to be affected by antibiotics. However, certain strains cannot be treated
by antibiotics, including Methicillin-resistant Staphylococcus aureus (MRSA) (Novick,2008). In
order to prevent infections, such as these, the spread of S. aureus infections must be understood.
This study expanded on the mechanisms behind this spread by examining the relationship
between the blood and nasal S. aureus isolates.
One mechanism of the spread is the quorum sensing system, which is the system that
allows S. aureus to communicate with other cells, control its virulence and form biofilms. This
system is encoded for by the agr locus, a two-component signaling unit that consists of a sensor
and a response regulator. The agr locus is comprised of the four genes agrD, agrB, agrC and
agrA. These four genes are able to control virulence by regulating the amount of toxins released.
Their interaction to bring about the regulation of virul0ence involves agrD being processed
through agrB and being secreted as an AIP (autoinducing peptide). The AIP then attaches to the
receptor agrC, where a phosphate is attached to the AIP. Afterwards, the AIP is transferred to
agrA, which activates transcription from the promoters P2 and P3. P2 allows the continuation of
the cycle; P3 causes the development of toxins. Therefore, a strain is identified as agr-defective,
or agr-negative, when agr expression through this interaction between the genes is no longer
carried through, and identified as agr-positive when agr expression is carried through.
In addition to the quorum sensing system, another mechanism of the spread is the
continued production of AIPs, or autoactivating peptides, by agr-defective strains. This

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mechanism was determined through a study that hypothesized that agr-defective S. aureus can be
transmitted and that they are mostly acquired at hospitals (Shopsin, 2008). As a result of testing
this hypothesis, it was determined that hemolytic and nonhemolytic strains only differ in one
locus and are therefore identified as congenic (Shopsin, 2008). It was theorized that this most
likely results from the fact that agr-defective strains derive from agr-positive stains. Furthermore,
it was observed that agr-positive strains generate a greater amount of exoproteins in comparison
to agr-defective strains (Shopsin, 2008). However, it was concluded that even though agr-
defective strains do not produce many exoproteins, they continue to produce AIPs. It was also
established that agr-defective strains are associated with hospitals, since all of the subjects that
had agr-defective strains had either indirectly or directly been associated with the hospital. Two
of the subjects were hospitalized, one had a sibling who was hospitalized, four were born at the
hospital and three were postpartum mothers (Shopsin,2008). In addition to this, it was concluded
that agr-defective strains can be transmitted as a result of seven cases in which a subject with
agr-defective strains had family members with S. aureus strains (Shopsin,2008). Therefore, the
hypothesis that agr-defective S. aureus was associated with hospitals and that agr-defective S.
aureus could be transmitted were supported. This study is significant, since agr-defective strains
are not usually present in healthy individuals. Hence, by knowing if agr-defective strains can be
transmitted, among whom they normally transmit and where they usually begin to colonize,
strategies can be developed to prevent them from colonizing, and in turn prevent S. aureus
infections from arising.
Mechanisms of the spread of S. aureus also include the transfer of S. aureus in the nose to
the bloodstream. To examine the relationship between S. aureus in the bloodstream and in the
nose, researchers involved in this study genotyped nasal and blood cultures with the use of
pulsed-field gel electrophoresis (PFGE ) (von Eiff, 2001). The sequences of the cultures were
then compared to determine if a relationship existed. It was concluded that the cultures from the
bloodstream and from the nose were identical, since 82.2% of the cultures from the bloodstream
were clones of the cultures from the anterior nares (von Eiff, 2001).
To expand on this mechanism of the spread of S. aureus infections, this experiment
examined the relationship between the agr-status and mutations of the cultures in the blood and
of the cultures in the anterior nares. The hypothesis of this experiment was that the S. aureus

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cultures in the blood originate from the cultures in the anterior nares. This hypothesis was
approached by examining the agr-status of the cultures, examining the mutations of the cultures
and determining the repeats of the cultures. An unexpected finding that came from this
examination of the agr-status of the cultures was that the agr-status of the colonies does not
influence whether or not those colonies will only colonize or will infect the body.
Materials and Methods:
Cell Cultures
The cell cultures used for the experiment were provided by Dr. Karsten Becker from
Universitätsklinikum Münster Institut für Medizinische Mikrobiologie. They were collected
during two different studies. In the first study, the isolates were obtained between November
1993 and September 1994 from the health care centers of thirty-two hospitals. These isolates
were collected from both the blood and the anterior nares of patients infected with S. aureus
bacteremia. The patients involved in this study had completed case-record forms that relayed
information about their date of birth, identification number and location in the hospital. In the
second study, the isolates were obtained between June 1994 and June 1999 from the anterior
nares of colonized patients. If the patients developed bacteremia during the course of the five-
year study, isolates from their blood were also collected. The types of cell cultures used for the
experiment included cultures from the blood and from the anterior nares of infected patients, and
cultures from the anterior nares of colonized patients. The cultures from the anterior nares of
colonized patients acted as controls. These cultures were placed in CYGP medium, snap frozen
with the use of dry ice and stored at -80 degrees Celsius. This was done because the cultures
needed to be placed in a setting where they were inactive to maintain their initial states. In
preparing these cultures, the frozen samples of the isolates were thawed, plated on GL plates and
maintained at 37 degrees Celsius in an incubator. The frozen samples were plated on GL plates,
since the strains needed to be “waken up” to proceed with genotyping them.
Dilution of the Blood and Nasal Cell Cultures
Bacterial dilution is the process of making a sample of colonies less concentrated. For
the dilution, 1 glass culture tube with 2 mL of the medium TSB, 1 eppendorf with 990 μL of
TSB, 1 eppendorf with 190 μL of TSB and 1 eppendorf with 133 μL of TSB were prepared
(Dilutions). The glass culture tube was then inoculated with a sample of isolates to a 0.5

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McFarland Standard. Afterwards, 10 μL from the glass culture tube was placed in the eppendorf
containing 990 μL of TSB, and 10 μL of the resulting mixture was placed in the eppendorf
containing 190 μL of TSB. Next, 7 μL of the resulting mixture was placed in the eppendorf
containing 133 μL of TSB. As each of these dilutions were completed, the mixtures were
thoroughly vortexed with the use of the Vortex Genie 2. 20 μL from the resulting solution was
then spread on warmed sheep blood plates to determine if the cultures were hemolytic,
nonhemolytic or mixed. If this process was not completed, there would have been too many
cultures. Having too many cultures would result in the overlapping of the cultures, which was
not ideal for the picking of individual cultures during the cross-streaking of the colonies.
Cross-streaking of the S. aureus Colonies
During the process of cross-streaking, a colony was chosen based on its hemolysis from
the 100 colonies produced by the 0.5 McFarland dilution. The plastic end of a sterile cotton swab
was then used to streak the strain RN4220, which produced a lot of beta-hemolysins, down the
center of a warmed sheep blood plate. Afterwards, the chosen colony was touched with the
plastic end of a sterile cotton swab, and streaked perpendicular to the strain RN4220. The sheep
blood plate was then maintained at 37 degrees Celsius in an incubator. By plating the culture
against a strain that produced a lot of beta-hemolysins, it could be determined whether or not the
culture released delta-hemolysins.
DNA Extraction of the S. aureus Colonies
To extract chromosomal DNA by mechanical lysis, the culture was first prepared by
inoculating broth with the culture. In inoculating the broth, a Bunsen burner was used to sterilize
a loop. The sterilized loop was then used to pick a single colony. The chosen single colony was
then placed in 2 mL of broth using a gentle twisting motion. The resulting broth was placed in a
shaking incubator at 37 degrees Celsius.
After the culture was prepared, 2 mL of it was spun down at 13.2 k for 10 minutes in an
Eppendorf 5415 centrifuge. Next, the supernatant was disposed of and the pellet was
resuspended in 300 μL of Tissue Cell Lysis Solution. The resulting mixture was then placed in a
bead beater tube filled with 1 mm of beads and beated at 6k for 20 seconds in a Savant FastPrep
bead beater machine. To pellet the beads, the tubes were then spun at 13.2 k for 10 minutes.
Once the beads were pelleted, the supernatant was aspirated using of a pipette and placed in a 1.5

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mL eppendorf with 150 μL of MPC Protein Solution. The tube was then overturned several times
and spun at 13.2 k for 10 minutes in the centrifuge. Following this, the supernatant was aspirated
and placed in a 1.5 mL eppendorf containing 500 μL of ice cold isopropyl. The eppendorf was
then overturned several times and spun at 13.2 k for 10 minutes in the centrifuge to pellet the
DNA. To thoroughly wash the DNA, the supernatant was disposed of, and the eppendorf was
filled with 500 μL of 75% ethanol and spun at 13.2 k for 5 minutes. This step was repeated
twice. Then, the ethanol was poured off, and the eppendorf was left to dry for 3 to 4 hours. After
the eppendorf had completely dried, the pellet was resuspended in 50 μL of distilled water.
This process for DNA extraction is designed to allow for breaking cells open, removing
lipids, proteins and RNA, and precipitating the DNA (DNA Extraction).
PCR of the Extracted DNA
To prepare for PCR, 2 μL of DNA was placed in a 25 μL master mix of nucleotides,
magnesium and tac polymerase, 19 μL of water, 2 μL of the forward primer and 2 μL of the
reverse primer. The forward and reverse primers used were made by vortexing a mixture of
either 10 μL of agrF or agrR aliquots and 240 μL of sterile distilled water. Once the mixture of
was created, it was placed in the Vapo.protect Eppendorf PCR machine.
Gel electrophoresis of the Blood and Nasal Colonies
Gel electrophoresis sorted the DNA by size and charge. To complete gel electrophoresis,
the gel was first made by heating a mixture of 50 mL of TBE and .5 g of agarose until it
appeared clear. When the temperature of the gel fell to 60 degrees Celsius, Ethidium bromide
was added to detect the DNA after gel electrophoresis was completed. After the Ethidium
bromide was thoroughly mixed into the gel, the gel was poured into a casting tray with stoppers.
Wells were then in the gel with a comb. Once the gel solidified, an adequate amount of buffer
was added. 5 μL of the ladder, of each of the DNA and of the dye mixtures were then loaded into
the wells. The gel electrophoresis was then turned on. The process confirmed if the DNA
amplified through PCR was the strand intended to be amplified by the number of base pairs that
appeared.
spa Typing of the S. aureus DNA
spa typing is the discrimination of the S. aureus for the sequencing of the DNA (Koreen,
2011). It involved finding and labeling the tandem repeats, the parts of the sequence that repeat

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themselves consecutively (Strommenger, 2006). Once all the tandem repeats were labeled, the
labels were placed in the order that the tandem repeats appeared.
Instead of spa typing, an alternate method that could be used in this experiment was
PFGE, or pulsed-field gel electrophoresis. PFGE broke up the large DNA molecules with the use
of an electric field (Joppa, 1992). MLEE, or multi-locus enzyme electrophoresis, could also be
used in place of spa typing. MLEE involved distinguishing the bacteria using cellular enzymes
(Chang Bioscience). However, spa typing was used instead of these methods because it
sequenced the DNA better and, therefore, discriminated it more effectively.
Statistical Analysis
After the data had been gathered, the results obtained for the strains from the blood were
placed next to the corresponding strains from the anterior nares to see if any correlation existed.
The characteristics of the strains that were primarily compared included their agr-status, their
gene sequence repeats and their mutations.
Results:
Bacteremia derives from the Staphylococcus aureus in the anterior nares.
Results showed that the agr-status of the isolates in the nose is the same as the agr-status
of the corresponding isolates in the blood, as shown by Figure 1a. This is supported by the fact
that the agr-status of both the nasal colonies and blood colonies in Patient #3 is positive. This
was established by plating the diluted samples of the cultures on sheep blood plates and by using
the method of cross-streaking, as illustrated by Figure 1b and 1c. Since the results showed that
thee agr-status of the nasal isolates and the corresponding blood isolates were the same, it was
concluded that bacteremia derives from S. aureus cultures in the nose.

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Patient # Nasal # Nasal cross-
streak
Blood # Blood cross-
streak
3 11 + 3 +
4 13 - 4 -
13 39 - 13 -
26 75 - 26 -
27 78 + 27 +
28 82 + 28 +
30 89 + 30 +
32 96 + 32 +
37 116 + 37 +
40 123 + 40 +
41 125 + 41 +
42 127 + 42 +
43 130 + 43 +
44 132 + 44 +
45 135 + 45 +
47 140 + 47 +
49 144 + 49 +
50 147 + 50 +
52 155 + 52 +
78 253 + 78 +
84 272 + 84 +
85 277 + 277 +
87 284 + 87 +
88 287 + 88 +
91 295 - 91 -
92 298 + 92 +
93 301 + 93 +
95 311 + 95 +
96 314 + 96 +
Figure 1a. The agr-status of isolates in the blood was the same as the agr-status of the
corresponding isolates in the anterior nares.
The agr-status of the isolates in the blood and in the anterior nares was determined by cross-
streaking the strains, as described in the Materials and Methods section. By cross-streaking, it
was determined that the agr-status of the isolates in the blood was the same as the agr-staus of
the nasal isolates, which implied that bacteremia derives from the nasal colonies.

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Figure 1b. Cross-streaking allowed for the determination of whether a strain was hemolytic
or not.
Cross-streaking showed whether or not a strain produced delta-hemolysins based on whether or
not there was a clearing. It also showed the strength of the strain’s hemolytic activity based on
the intensity of the clearing.
Figure 1c. The agr-status of the blood isolates and of the nasal isolates was compared with
the use of cross-streaking.
Cross-streaking visually showed the correlation between the agr-status of cultures from the blood
and cultures from the anterior nares.

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As well as showing that the agr-status of the blood isolates and the nasal isolates was the
same, the results supported the conclusion that the S. aureus isolates in the blood derived from
the S. aureus isolates in the anterior nares by demonstrating that the mutations that occurred in
the blood colonies were the same as the mutations that occurred in the corresponding nasal
colonies, as shown by Figure 2a. This was determined with the use of spa typing, a procedure
described in the Materials and Methods section. The three types of mutations that were found
included single-nucleotide polymorphism (SNP), insertion sequence (IS), base pair insertion (+)
and base pair deletion (-), as shown by Figure 2b. Single-nucleotide polymorphism occurred
when a nucleotide in a genome differed within the paired chromosomes (SNP Fact Sheet). A
DNA sequence was identified as an insertion sequence if it was short and could move in the
genome (Schoenmakers, 2010). Base pair insertion occurred when nucleotide base pairs were
added in a DNA sequence, and base pair deletions occurred when nucleotide base pairs were
removed from a DNA sequence (Leong, 1985). These mutations are significant because they
influenced gene expression.
Patient # Nasal # Nasal Mutation Blood # Blood Mutation
4 13 118-IS256 4 118-IS256
13 39 t551a 13 t551a
26 75 a409 (-1 bp) 26 a409 (-1 bp)
78 253 c771t, c583t 78 c771t, c583t
91 295 t313 (+1 bp) 91 t313 (+1 bp)
143 466 c461a 143 c461a
147 484 a86c 147 a86c
171 564 t352 (+1 bp) 171 t352 (+1 bp)
180 595 g571a 180 g571a
Figure 2a. The mutations that occurred in the isolates in the blood were the same as the
mutations that occurred in the nasal isolates.
The mutations that occurred in both the blood and the nasal isolates were found with the use of
spa typing, as described in the Materials and Methods section. As a result of spa typing, it was
determined that the mutations in the isolates in the blood and in the corresponding nasal isolates
were the same.

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Figure 2b. Three types of mutations were identified in several of the isolates.
The three types of mutations that were found in the isolates were base pair insertion, base pair
deletion, single-nucleotide polymorphism and insertion sequence.
In addition to showing that the mutations in the blood and nasal isolates were the same,
the results supported the fact that bacteremia derived from nasal isolates by showing that the
genetic sequences of the cultures from the blood and the corresponding cultures from the anterior
nares were the same, as shown by Figure 3.
Colonies IS Element SNP BP Insertion/
Deletion
Blood 2 4 2
Nasal 1 3 4

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Patient # Nasal # Nasal Repeats Blood # Blood Repeats
1 4 UJGGBBGGJAGJ 1 UJGGBBGGJAGJ
2 8 YGFMBQBLQBLPO 2 YGFMBQBLQBLPO
3 11 WGKAKAOMQQ 3 WGKAKAOMQQ
4 13 YHFGFMBQBLO 4 YHFGFMBQBLO
5 18 UJGBBGGJAGJ 5 UJGBBGGJAGJ
6 21 ZDGMDMGMM 6 ZDGMDMGMM
10 30 XKAKB 10 XKAKB
11 35 UBGGJAGJ 11 UBGGJAGJ
12 37 ZFGU2DMGGM 12 ZFGU2DMGGM
14 42 XKAKBEMBKB 14 XKAKBEMBKB
15 44 YGFMBQBLPO 15 YGFMBQBLPO
16 47 XKAKBEMBKB 16 XKAKBEMBKB
18 51 UJFMEBKBPE 18 UJFMEBKBPE
19 54 WGKAKAOM 19 WGKAKAOM
20 57 YHGFMBQBLO 20 YHGFMBQBLO
21 59 YHGFMBQBLO 21 YHGFMBQBLO
22 61 WGKAKAOMQ 22 WGKAKAOMQ
26 75 ZDGMDMGMMM 26 ZDGMDMGMMM
27 78 I2Z2DZ2EGMMJH2M 27 I2Z2DZ2EGMMJH2M
28 82 YGFMBQBLO 28 YGFMBQBLO
30 89 ZFGU2 30 ZFGU2
32 96 UJFMEBKBPE 32 UJFMEBKBPE
37 116 I2Z2EGMMJH2M 37 I2Z2EGMMJH2M
40 123 WGKAKAOMQQQ 40 WGKAKAOMQQQ
42 127 YHFGFMBQBLO 42 YHFGFMBQBLO
Figure 3. The genetic sequences of the isolates from the blood and from the anterior nares
were the same.
The genetic sequences of both the nasal and blood cultures were determined with the use of spa
typing. Since the genetic sequences of the nasal isolates and of their corresponding blood
isolates were the same, it was concluded that the blood cultures derive from the nasal cultures.
agr-status of Staphylococcus aureus isolates in patients does not affect the probability of
becoming infected with Staph.
Results showed that the agr- status of S. aureus colonies in patients is not a determining
factor of whether or not the patients become infected with Staph. The results indicated this, since

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the percentage of agr-defectives in the nasal and blood isolates from infected patients was the
same as the percentage of agr-defectives in the nasal isolates from non-infected patients. This
implied that agr-defectives can as easily colonize infected patients as they can colonize non-
infected patients.
Infecting Non-Infecting
agr-status Nasal
(188)
Blood
(231)
Nasal
(209)
agr (+) 175 210 187
agr (-) 13 21 22
%agr (-) 6.91 9.09 10.53
Figure 4. The agr-status of S. aureus isolates did not influence whether or not a patient was
infected with Staph.
The percentage of agr-defectives in the nasal and blood isolates of infected patients was similar
to the percentage of agr-defectives in the nasal isolates of non-infected patients.
Discussion:
The goal of this experiment was to determine if the isolates from the blood derive from
the nasal isolates. The results showed that the hypothesis that colonies from the blood derive
from nasal isolates was supported. This is due to the fact that the agr-status of the isolates in the
blood and of the isolates in the anterior nares was the same. The mutations and repeats of the
isolates from both areas of colonization were the same as well. In addition to this, the results
showed that the agr-status of S. aureus strains does not influence whether or not it will infect a
patient. These results reinforced the results of the study completed by von Eiff in 2001, which
also concluded that the isolates from the blood and the nose were related by implementing
similar techniques to those used in this study. These results are significant due to the fact that a
large number of people carry Staphylococcus aureus on a regular basis.
About 25% to 30% of people carry Staphylococcus aureus isolates, and a large number
of them carry strains that often modify themselves. Although these isolates are more dangerous
to breastfeeding women, people with diabetes, people with cancer, and children, they are
commonly present in everyone. Therefore, many are susceptible to Staphylococcus aureus
infections, since it was found that they derive from the colonies in the anterior nares. As a result
of this, the nasal colonies must be eliminated to reduce the number of infections caused by
Staphylococcus aureus and, in turn, stop the cycle of transfer.

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To eliminate the nasal colonies, they must be treated with an ointment. The nasal
ointment that is currently the most commonly used is mupirocin, a topical antibiotic that is not
useful in acting against viral or fungal infections. It reduces the number of infections caused by
Staphylococcus aureus by prohibiting protein synthesis. As documented by Wertheim, mupirocin
allows for the elimination of 91% of the nasal colonies (Wertheim, 2004). In addition to
mupirocin, bacitracin and rifampin may be used to eliminate the nasal colonies. However, they
are not as effective, since rifampin only eliminates 79% of the nasal colonies, while bacitracin
only eliminates 44% of the nasal colonies.
To expand on this study, mupirocin should be further examined. This is because although
mupirocin supports a reduction in the prevalence of bacteremia, it is not highly effective. As
shown by Rahman’s study, several strains of Staphylococcus aureus have developed that are
highly resistant to mupirocin (Rahman, 1988). Mupirocin is also not highly effective because it
does not prevent the colonization of extranasal locations and usually results in colonization with
exogenous strains. Therefore, a study can be conducted to develop a more efficient way of
eliminating the isolates in the anterior nares.
This more efficient way of eliminating the isolates in the anterior nares will most likely
involve disrupting the quorum sensing system because the quorum sensing system allows S.
aureus to communicate with other cells, control its virulence and form biofilms, which are
groups of microorganisms found on solid substrates (Teng,2011). Biofilms are created when
free-floating microorganisms attach to a surface and begin dividing or incorporating other
microorganisms (Yarwood, 2004). Being a part of these structures are beneficial for bacteria,
since they provide security by heightening the resistance to detergents and antibiotics
(Yarwood,2004). This quorum sensing system regulates these functions of S. aureus with the
accessory gene regulator (agr) locus.
The agr locus reduces the expression of surface proteins and increases the expression of
exotoxins (Shopsin,2008). Therefore, it supports S. aureus’s expression of virulence and adds to
the severity of infections, such as murine subcutaneous abscesses, which are abscesses situated
beneath the skin. The agr locus assists S. aureus’s expression of virulence and heightens the
severity of infections by encoding for the secretion of AIPs, or autoactivating peptides (Muir,
2009). AIPs are types of autoactivators, which are molecules that induce their own synthesis

16
(Geisinger,2008). Their density is correlated with the local population. This means that as the
local population increases, the density of AIPs increases, which is significant due to the fact that
once the density of the AIPs reaches a certain amount, the entire population coordinates and acts
as one (Muir, 1216). An example of bacteria’s use of AIPs to coordinate is bioluminescence,
since bioluminescent bacteria only glow when their density is high enough (Geisinger, 2008).
Variations in AIPs arise from variations in their ogliopeptide sequences (Ji,2011). These AIPs
are administered by agrD. agrD is only one of the four genes in the operon of the agr locus,
which also consists of agrB, agrC and agrA..
Variations in the agr locus derive from differences in the AIPs, agrB and agrC. The
different agr loci are categorized into four agr specificity groups (Jarraud, 2000). These
variations in the agr locus originate from heterologous interactions between the AIP and agrC.
This is because the heterologous interactions between the AIP and agrC lead to the interference,
which, in turn, results in a change in the accessory gene expression (Muir,2009). Therefore, the
isolates in the anterior nares can be disrupted by obstructing agrC and agrB.
In addition to this research based on determining a more efficient way of eliminating
isolates in the anterior nares, research can be done to determine if bacteremia also derives from
S. aureus colonies on other sites of the body besides the anterior nares, such as other mucous
membranes and the skin. This would allow for the full examination of the derivative of infections
caused by Staphylococcus aureus.
Acknowledgements:
I would like to thank all the people that helped make the completion of this project
possible. I would first like to thank Mr. Richard Lee for encouraging me to participate in the
research program, for helping me find a lab suitable to my interests, and for supporting me in the
writing of this paper. I would also like to thank those that helped me in the Skirball Institute at
New York University. I would particularly like to thank Dr. Richard Novick for providing me
with the opportunity to work at the lab and Dr. Bo Shopsin and Mr. Gregory Wasserman for
guiding me in completing this project and making the experience at lab pleasant. Without the
support of Dr. Bo Shopsin and Mr. Gregory Wasserman, this project would not have been
achievable.

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