Chlamydia

=__**Disease/Drug of interest** : __ Chlamydia/Azithromycin =

**Motivation and Background** :
 Chlamydia is the most prevalent infectious disease in the United States, with nearly 3 million cases reported every year [1]. Chlamydia is caused by the bacterium //Chlamydia trachomatis//, and is mainly spread by vaginal, oral, or anal sex. In addition, chlamydia can be passed down from a mother to child during childbirth [1]. If left untreated, chlamydia can cause pelvic inflammatory disease in women, causing damage to occur to the fallopian tubes, potentially causing infertility [1]. Furthermore, it can cause ectopic pregnancy or premature birth [1]. In males, untreated cases of chlamydia may cause nongonococcal urethritis, epididymitis, or proctitis [1]. If a child contracts chlamydia during childbirth, he or she could have eye infections (such as pink eye), suffer from blindness, or have pneumonia [1]. Because chlamydia is a sexually transmitted disease, men and women who are more sexually active are more at risk for chlamydia. Chlamydia has also shown to be more prevalent among young women, minorities, and people of poor socio-economic condition [2]. Chlamydia often will not cause obviously noticeable symptoms, causing affected individuals to not seek treatment, allowing the disease to manifest within the body and spread unnoticed. Because of this, chlamydia has remained the most common sexually transmitted disease despite the availability of effective treatment [1].  //Chlamydia trachomatis// is a spherical bacterium (0.2 µm- 0.4 µm in length) different from other bacteria as it lacks a peptidoglycan cell wall and is instead an intracellular parasite, meaning it requires other growing cells to remain viable [3]. In addition, it is gram negative, affecting how it is treated [4]. Despite its many differences from the average bacterium, //C. trachomatis// still contains both DNA and RNA, has its own ribosomes, and multiplies using binary fission [3]. //C. trachomatis//, when engulfed by a host through phagocytosis, prevents the fusion of the phagosome and lysosome, which normally occurs to digest any ingested particles. Afterwards, the bacterium secretes glycogen and transforms into a reticulate body, which parasitically obtains energy from the host, allowing it to reproduce and create more reticulate bodies. After 24 hours, reticulate bodies displace the host’s nucleus, and after continual growth of the reticulate bodies, the host will burst, releasing infective elementary bodies [3].

[[image:http://www.mdpi.com/molecules/molecules-20-04180/article_deploy/html/images/molecules-20-04180-g001-1024.png width="606" height="420"]]

 * Figure 1: ** Representation of developmental cycle of //C. trachomatis //[5]. EB stands for elementary bodies and RB stands for reticulate bodies.

Although it seems that chlamydia is a well-understood disease with an effective cure (as discussed in later sections), it is imperative that money is dedicated to furthering our understanding of chlamydia. Chlamydia often doesn't display symptoms, allowing it to lurk within the bodies of many unaware individuals. Not only does this allow this disease to negatively affect the lives of innumerable affected individuals and their loved ones by inflicting severe damage to his or her internal tissue, but can pose a much bigger threat to the health of the human population as a whole. Bacteria contain plasmids (small circular pieces of DNA that are separate from their genome) that allow them to gain additional characteristics by taking up additional plasmids [7]. Bacteria are capable of acquiring new DNA in many methods, but the most problematic for us is transduction, where bacteria transfer plasmids to each other, allowing them to pass on a variety of characteristics, including antibiotic resistance [7]. Due to the widespread nature of //C. ////trachomatis,// it is possible this bacteria could be acting as an underground messenger between bacteria, transferring genes when an individual is unknowingly affected by //C. trachomatis// and another bacterial disease [7]. Research needs to be conducted to help chlamydia detection to be much easier, as current methods require laboratory tests that many individuals do not take. Earlier detection is the key to fighting many of the negative affects chlamydia poses to our society.

1. Center for Disease Control and Prevention. http://www.cdc.gov/std/chlamydia/-stdfact-chlamydia.htlm (accessed February 7, 2016). 2. Malhotra, M.; Sood, S.; Mukherjee, A.; Muralidhar, S.; Bala, M., Genital Chlamydia trachomatis: An update. Indian Journal of Medical Research 2013, 138, (3), 303-316. 3. School of Biological Sciences. University of Texas at Austin. http://web.biosci.utexas.edu/field/mic361a/mic361/chlamydi.html (accessed February 6, 2016). 4. Backheti, H.; Al-Hadiya, B.; Abd-Elgalil, A., Azithromycin 2014, 39, (1), 1-40. 5. Potroz, M.; Cho, N., Natural Products for the Treatment of Trachoma and Chlamydia trachomatis 2015, 20, (3), 4180-4203. 6. National Information Program on Antibiotics. Azithromycin. http://www.antibiotics-info.org/azithromycin.html (accessed 28 February 2016). 7. Hartwell, L.; Hood, L.; Goldberg, M.; Reynolds, A.; Silver, L., //Genetics: From Genes to Genomes//, 5th ed.; McGraw Hill: Boston, 2003.
 * References: **

**External links:**
<span style="font-family: 'Times New Roman',Times,serif;">1. http://www.antibiotics-info.org/azithromycin.html <span style="font-family: 'Times New Roman',Times,serif;">2. <span style="font-family: 'Times New Roman',Times,serif;">http://www.cdc.gov/std/chlamydia/stdfact-chlamydia.htm

=__**Target Information** : __=

[[image:http://www.antibiotics-info.org/images/azithromycin_clip_image004.jpg]]
<span style="font-family: 'Times New Roman',Times,serif;">**Figure 2:** Cartoon representation of Azithromycin binding to the 50S subunit of a bacterial ribosome [6].

<span style="font-family: 'Times New Roman',Times,serif;">**Size:** The target of Azithromycin is the 50S subunit of the bacterial ribosome, which complements the 30S subunit in forming an active ribosome. The mass of the active ribosome is 2.5 MDa, or 2.5e6 Da.

<span style="font-family: 'Times New Roman',Times,serif;">**Location:** The bacterial ribosomes are found inside //C. trachomatis//, which are located inside human cells during infection due to the intracellular parasitic nature of //C. trachomatis//.

<span style="font-family: 'Times New Roman',Times,serif;">**Function in a normal cell:** Bacterial ribosomes are not found in normal human cells, and therefore do not have a function in the human body. In a normal bacterial cell, the ribosomes are used to synthesize proteins that carry out essential functions for the cell, allowing it to grow and assemble more reticulate bodies to be released as future bacteria.

=__**Drug Information**** : **__=

<span style="font-family: 'Times New Roman',Times,serif;">**Figure 3:** Schematic representation of Azithromycin [6].
 * Schematic figure of drug **

<span style="font-family: 'Times New Roman',Times,serif;">**Formula:** C38H72N2O12

<span style="font-family: 'Times New Roman',Times,serif;">**Molecular weight:** 748.984 g/mol

<span style="font-family: 'Times New Roman',Times,serif;">**CAS Number:** 83905-01-5

<span style="font-family: 'Times New Roman',Times,serif;">**Delivery method:** Pill <span style="font-family: 'Times New Roman',Times,serif;">**Side effects:** The main side effects of azithromycin include: anorexia, dizziness, nausea, drowsiness, and changes in taste or smell. Lesser side effects include: anxiety, renal failure, insomnia, hepatitis, and photosensitivity.

<span style="font-family: 'Times New Roman',Times,serif;">**Other names:** Another common name for azithromycin is its original market name, "Zithromax." <span style="font-family: 'Times New Roman',Times,serif;">**Maker or company:** Pfizer <span style="font-family: 'Times New Roman',Times,serif;">**Is it patented?** Yes <span style="font-family: 'Times New Roman',Times,serif;">**Clinical Trials Info:** Clinical trials have been performed to test the effectiveness of azithromycin. Analysis of twelve random clinical trials by the CDC showed that azithromycin has a success rate of 97% in curing chlamydia, and is considered extremely effective. 321 clinical trials involving azithromycin have been conducted that explore a variety of other interactions between azithromycin and the human body, such as whether or not azithromycin affects pregnant woman differently.

__** Origin ** : __ <span style="font-family: 'Times New Roman',Times,serif;">Azithromycin was first discovered at Pliva, a Croatian pharmaceutical company, in 1980, and was patented the following year. Azithromycin is created by preparation from erythromycin, which is produced from the bacteria Saccharopolyspora erythraea. A decade after its discovery, the biopharmaceutical company, Pfizer, brought azithromycin to the market under the name Zithromax.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Doxycycline is the most common alternative to azithromycin. It functions similarly to azithromycin, but targets the smaller 30S ribosomal subunit. It is deemed 'equally efficacious' by the CDC, but is less commonly used due to the stricter dosage regime.
 * Alternatives to this drug ** :

<span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Azithromycin is effective against many gram negative bacteria. Azithromycin is also commonly used to cure many other bacterial infections, including typhoid, strep throat, sinusitis, bronchitis, pneumonia, and ear infections. Furthermore, azithromycin is commonly used to treat babies and individuals with weaker immune systems.
 * Other uses ** :