Antibiotic Resistance: Horizontal Gene Transfer

[vc_row][vc_column][vc_column_text] Antibiotic Resistance: Horizontal Gene Transfer Robert Lo, Ph. D, D.V.M. Antimicrobial compounds, including both naturally and chemically synthesized compounds, have been one of the most important inventions to combat infections. Penicillin was the first natural antibiotic to be discovered from Penicillium fungus by Alexander Fleming in 1928. Following the discovery of penicillin, researchers started search for more antibiotics from soil microorganisms, including bacteria and fungi. Streptomycin produced by Streptomyces griseus was found in 1943. Most antibiotics in use today originated from the phylum Actinobacteria with nearly 80% of actinobacterial-derived antibiotics produced by soil-dwelling bacteria of the genus Streptomyces (Barka et al., 2016). Currently, antibiotics are classified into different groups based on their mechanism of antimicrobial activity. The main groups are: inhibit cell wall synthesis (β-lactams and glycopeptides), depolarize cell membrane (lipopeptides), inhibit protein synthesis (aminoglycosamides, chloramphenicol, lincosamides, macrolides, oxazolidinones, streptogramins, and tetracyclines), inhibit nucleic acid synthesis (Quinolones), inhibit fatty acid synthesis (platensimycin), and inhibit metabolic pathway (sulfonamides and trimethoprim). With so many groups of antibiotics to treat pathogens, it seems that antibiotics would win the battles against the infection. However, the marked increase of antibiotics resistance pathogens have exceeded new drug discovery, and this resistance occurs shortly after a new drug is approved for treatment. Therefore the emergence and spread of antibiotic resistance among pathogenic bacteria has raised the concerns for public health worldwide. How did antibiotics resistance pathogens appear so quickly? More importantly, how did resistance develop? Antibiotic resistance is ancient and it is expected results of the interaction of many organisms with their environment. Since most antimicrobial compounds are produced by bacteria, it is nature that those antibiotic-producing bacteria also contain self-resistance mechanisms against their own antibiotics. D’Costa et al. identified that most Streptomyces are resistant to an average of seven to eight antibiotics, including newly developed and clinically important therapeutics (D’Costa et al., 2006). In addition, it is believed that non-antibiotics producing environmental bacteria have evolved resistance mechanisms to overcome the action in order to survive via co-existence with antibiotic-producing bacteria. Researchers also identified the presence of gene-encoding resistance to β-lactams, tetracycline, and glycopeptide antibiotics in metagenome samples of 30,000-year-old permafrost (D’Costa et al., 2011). Analysis of the vancomycin resistance gene cluster in this metagenome also revealed conservation of gene sequence and synteny with modern resistance clusters in the clinic as well as protein function and structure. Resistance to antibiotics occurs either by mutation or by acquisition of resistance genes via horizontal gene transfer. It is believed that horizontal gene transfer is the most important factor in the current pandemic of antimicrobial resistance. Though the mechanisms has long been existence, the rate of antibiotic resistant gene spread and the number of resistant strains has increased tremendously over the past few decades because of selective pressure through antibiotic use. The use and misuse of antibiotics in medicine, agriculture, and aquaculture has been linked to the emergence of resistant bacteria (Cabello, 2006; Economou & Gousia, 2015). In addition, the majority of consumed antibiotics are excreted unchanged, and are then introduced into the environment directly or through waste streams (Sarmah et al, 2006). As a result, waste streams become hotspots for the spread of antimicrobial resistance because of the introduction of antibiotic selection pressure into commensals and pathogens (Graham et al., 2011). These increasing environmental exposure to antibiotics has significantly increased antibiotic resistance genes of pathogenic bacteria, especially with the tetracycline resistance gene being 15 times more abundant now than in the 1970s (Knapp et al., 2010). In addition, increasing selection pressure has accelerated bacterial horizontal gene transfer process, increasing the number of resistome elements which reside mobile DNA compared to the pre-antibiotics era (Datta and Hughes, 1983). Role of horizontal gene transfer in spread of antibiotic resistance genes Conjugation Conjugation is the process by which one bacterium transfers genetic material to another through direct contact. In conjugation, DNA is transferred from one bacterium to another. After the donor cell pulls itself close to the recipient via cell surface pili or adhesins, DNA is transferred between cells. Plasmid- mediated conjugation is considered the most prevalent method of horizontal gene transfer mechanisms in nature (Volkova et al., 2014). The acquisition of novel genes by plasmids through mobile genetic elements such as transposons (Babakhani and Oloomi., 2018) or integrons (Akrami et al., 2019), and their ability to replicate in a wide range of hosts, made them perfect vectors for the spread of AMR. Some of known plasmids-mediated antibiotic resistance gene transfer events are the spread of carbapenemase blaCTX-M extended-spectrum β-lactamases (ESBLs), which can hydrolyze β-lactams (Ramos et al., 2013), and spread of quinolone resistance gene (Robicsek et al., 2006). Transposons are found in both gram negative bacteria, including Tn1, Tn3, Tn5, Tn9, Tn10, Tn21, Tn501, Tn903, Tn1525, Tn1721, Tn2350 and Tn3926, and gram positive bacteria, including Tn551, Tn917, Tn4001, Tn4451, and Tn4003. Resistance gene cassettes most frequently associated with class 1 integrons are streptomycin-spectinomycin resistance genes and trimethoprim resistance genes. Class 1 integrins has been found in gram negative bacteria, including Escherichia, Klebsiella, Aeromonas, Enterobacter, Providencia, Mycobacterium, Burkholderia, Alcaligenes, Campylobacter, Citrobacter, Stenotrophomonas, Acinetobacter, Pseudomonas, Salmonella, Serratia, Vibrio, and Shigella (Partridge et al., 2009; Xu et al., 2011 ), and in gram positive bacteria, including Corynebacterium, Aeromonas, Staphylococcus, Streptococcus, Enterococcus, and Brevibacterium (Nandi et al., 2004; Xu et al., 2010). Class 2 integrons have been found in Salmonella, Enterobacteriaceae, Enterococcus, Acinetobacter, and Pseudomonas (Machado et al., 2008; Xu et al., 2010; Xu et al., 2011). Class 3 integrons have been reported in Escherichia, Citrobacter, Klebsiella, Salmonella, Pseudomonas, Acinetobacter, Alcaligenes, and Serratia (Rowe-Magnus et al., 2001; Ploy et al., 2003). Class 4 integrons have been linked to Pseudomonas, Vibrionaceae, Xanthomonas, Shewanella, and other proteobacteria (Clark et al., 2000; Rowe-Magnus et al., 2001). Transformation In transformation, a bacterium takes in DNA from its environment, often DNA that has been shed by other bacteria. If the DNA is in the form of a circular DNA called a plasmid, it can be copied in the receiving
Breed-related disease: British Shorthair Cat

John K. Rosembert The British Shorthair is a dignified, intelligent and affectionate companion. They aren’t your general lapcat, but they tend to be always by your side on the sofa or at least nearby. Females tend to have a serious demeanor, while males are more happy -go-lucky. These laidback cats can get along well with dogs and are calm around children, but they don’t enjoy being hauled around. The British Shorthair is solid and muscular with an easygoing personality. As befits his British heritage, he is slightly reserved, but once he gets to know someone he’s quite affectionate. His short, dense coat comes in many colors and patterns and should be brushed two or three times a week to remove dead hair. British Shorthairs are generally a robust breed without too many problems. Because they have been bred with Persians in the past there is small chance of a being affected by: Polycystic kidney disease: a condition where cysts, present in the kidneys from birth, gradually increase in size until the kidney cannot function normally, resulting in kidney failure. A genetic test is available for this disease. Hypertrophic cardiomyopathy: a condition where the volume of blood that the heart pumps with each contraction is reduced. This can cause fainting, tiredness and other signs of heart disease. Sources: http://www.vetstreet.com/cats/british-shorthair#1_ugw20zmq http://aubreyamc.com/feline/british-shorthair/ Photo credit: https://www.pdsa.org.uk/taking-care-of-your-pet/looking-after-your-pet/kittens-cats/british-shorthair Photo credit: https://apkpure.com/tw/british-shorthair-cat-wallpaper-hd/com.autoinsurance.australia#com.autoinsurance.australia-1
Breed-related disease: Labrador Retriever

John K.Rosembert The Labrador Retriever (aka Labrador, or Lab for short) is one of several kinds of retriever, a type of gun dog. The Labrador Retriever is loyal, devoted, playful, and hardworking. He is patient with children and makes a wonderful companion and family dog. There are two types depending on which lab they were bred from: the English-bred Labs and the American-bred Labs. The English-bred Labs have a stockier, blockier, heavier and thicker build than the American-bred dogs. Both breeds have smooth double-coats without waves. The English labs also are more laid-back and they mature faster. Whatever their ancestry, Labs have a natural disposition to please and have fun, Although he barks protectively, due to his friendly nature, he is not suitable to be a guard dog, but he excels as a guide dog or assistance dog for the disabled, a search-and-rescue dog and a sniffer dog. If you are thinking of getting or got a Labrador Retriever, here are some of the most common health issues your Labrador might face: Joint Problems: Many Labs suffer from joint problems such as hip or elbow dysplasia, these conditions affect the hip or elbow joints, prohibiting normal movement and causing pain and immobility. Bloat and Obesity: Labradors are famously known for rapid eating which can also result in dangerous gastric distention. In dogs, this is also known as bloat which is a huge health problem in Labradors. Caudal myopathy: This condition, which can scare many Labradors Retriever owners, is also known as “limber tail syndrome” and is commonplace among the breed, but not exclusive to it. Myopathy in this area is characterized by a flaccid paralysis in the tail. Eye problems: Many Labradors suffer from eye problems, from minor ocular defects to cataracts or progressive retinal atrophy. These are hereditary diseases that impair the dog’s vision. Sources: Photo Credit: http://fishsubsidy.org/labrador-retriever/ https://www.dogzhealth.com/labrador-retriever-health-problems/ https://www.labradortraininghq.com/labrador-health-and-care/common-labrador-health-conditions/ https://labrador-central.com/labrador-health-issues/.
Breed-related disease: Persian Cat

John K. Rosembert The Persian is the most popular pedigreed cat in North America, if not the world, it is also known as the “Persian Longhair” in the English-speaking countries. In the Middle East region, they are widely known as “Iranian cat” and in Iran they are known as “Shiraz cat”. The first documented ancestors of the Persian were imported into Italy from Iran around 1620. The Persian comes in two types: show and traditional. The show Persian has a round head enhanced with a thick ruff, small ears, a flat nose, big round copper eyes, a broad, short body with heavy boning atop short tree-trunk legs, and a thick, flowing plume of a tail. While the traditional Persian, also known as the Doll Face, does not have the extreme features of the show Persian, and his nose is a normal length, giving him a sweet expression. Both types have a long, glamorous coat that comes in many colors and patterns, and both share the same wonderful personality. Persian cats suffer from certain recurring problems. This does not mean that Persian cats are necessarily unhealthy, but you should be aware of their risks and needs in order to prevent diseases and notice them in time. Here are some of the most common diseases of Persian cats …. Hairballs and trichobezoars: Persian cats are known for their long and dense coat. Therefore, they are more likely to suffer from trichobezoars than other cats with shorter hair. Trichobezoars are hairballs that form in the cat’s stomach and digestive tract. Cats can usually regurgitate hairballs, but occasionally they accumulate in the stomach. When this happens, cats suffer badly and may even have serious health consequences. Polycystic kidney disease: Persian cats are very prone to polycystic kidney disease. This means that cysts develop in the kidney area, growing and multiplying if left untreated. It is estimated that 38% of Persian cats suffer from this hereditary disease. Respiratory problems: Persian cats are easily recognizable for their flat face and huge, round eyes. Sadly, having such a small nose causes the nasal passage to be very short and more sensitive to the cold, heat, moisture or dry environment. Heart problems: Fewer than 10% of older Persian cats have been found do have Hypertrophic cardiomyopathy which causes an enlargement of the left heart chamber and can result in sudden death. Eye problems: The special shape of a Persian cat’s eyes can also cause problems. The most common ocular diseases of Persian cats include: Congenital ankyloblepharon which is an inherited abnormality that usually occurs in blue-eyed Persian cats. Congenital epiphora consists of an excessive tearing of the tear duct, which results in oxidation of the hair around the eyes and infection by bacteria or fungi in the affected area Entropion is when the eyelashes rub and irritate the cat’s cornea as a result of the inversion of the eyelid edge Primary glaucoma Excessive blood pressure in the eye which results in opacity and vision loss. It should be treated by surgery. Sources: Photo credit: https://www.animalwised.com/common-diseases-of-persian-cats-738.html https://en.wikipedia.org/wiki/Persian_cat Persian https://www.animalwised.com/common-diseases-of-persian-cats-738.html