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CDC is not responsible for Section compliance accessibility on other federal or private website. Cancel Continue. In other bacteria, efflux pumps have been demonstrated to mediate resistance against host-derived antimicrobial peptides, which are an important aspect of the host innate immune system Shafer et al. It is possible that this mechanism plays a similar role in the virulence of K. Present in several Gram-negative species, the T6SS has been shown to target both other bacteria as well as eukaryotic cells, suggesting a dual role in both competition and pathogenesis.
Bioinformatic analysis of K. More recent studies have begun to characterize T6SS effectors in K. In hypervirulent strain Kp T6SS secretion systems appear to be present in both the core and accessory genome, promote competition with other bacteria in sites of colonization, and enhance fitness in sites of infection. The Centers for Disease Control and Prevention estimates that more than two million people contract infections due to antibiotic-resistant microorganisms each year in the United States.
There are multiple factors believed to contribute to the spread of antibiotic resistance, including inappropriate antibiotic use in healthcare and agriculture, and lack of new antimicrobial therapeutics CDC, Several mechanisms of antibiotic resistance are found in K. Colonization with antibiotic-resistant K. The accessory genome is central to antibiotic resistance in K. Alexander Fleming was the first to note that E. For example, SHV is consistently found in the chromosome, and corresponding ampicillin resistance is a hallmark of the species Babini and Livermore, ; Bialek-Davenet et al.
ESBL-producing K. ESBLs are able to hydrolyze oxyimino-cephalosporins, such as third-generation cephalosporins and aztreonam, but are inhibited by clavulanic acid Bush et al. Therefore, ESBLs are tightly linked to other accessory genes that could improve fitness of the strain it is in. And plasmid-based resistance mechanisms are associated with certain lineages that may have a characteristic accessory genome.
For instance, a recent study identified that K. Carbapenems have typically been the drug of choice to treat severe infections caused by ESBL-producing bacteria. Perhaps due to the selective pressure of treating ESBL infections with carbapenems, carbapenem resistance has emerged and K.
Carbapenem resistance is primarily driven by the accessory genome, sometimes in combination with mutations in the core genome. Carbapenem resistance in K. For instance, hyperproduction of an ESBL or AmpC enzyme combined with a porin mutation can lead to a resistance phenotype, particularly to ertapenem Bradford et al. The most worrisome mechanism of carbapenem resistance is through plasmid-mediated carbapenemases.
The association between the KPC gene and certain clonal groups suggests that these resistance plasmids have become stable members of the accessory genome in certain K. Additional types of carbapenemases have also emerged in the K. MBLs are characterized by a requirement for zinc at their active site and infections with MBL-producing strains are frequently associated with travel to and hospitalization in endemic regions van der Bij and Pitout, For example, NDM-1 was discovered in a K.
Since then, acquisition of NDM-1 isolates has been strongly associated with individuals of Indian descent who travel to or live in the Indian subcontinent Yong et al. VIM-encoding isolates are endemic to Greece and Italy, and infections in the United States are associated with travel to and been hospitalization in these countries Lauretti et al. VIM variants bla VIM are carried on integrons that can be integrated into either the chromosome or carried on plasmids Lauretti et al.
OXA carbapenemases are class D enzymes are characterized by their ability to hydrolyze cloxacillin or oxacillin Bush and Jacoby, Colistin resistance in K. Colistin is among the polymyxin class of antibiotics, used to treat Gram-negative infections in the s and s.
Their use was discontinued due to renal- and neurotoxicity Jerke et al. However, the recent emergence of CRE has made it necessary to return to colistin as a drug of last resort.
In , plasmid-mediated resistance to colistin was discovered in an E. This discovery heralds the potential for easily transmissible genes leading to pan-resistance. The prevalence of mcr-1 in K. The first reported incidence of mcr-1 in the United States occurred in in E. In September of a pan-resistant isolate of K. Similar to recent findings across K. A prospective study determined that patients colonized with antibiotic-resistant K.
They further compared serotypes of colonization isolates and subsequent infecting isolates, finding that 14 of 31 For CR-Kp, colonization can persist and spread silently for years in long-term care facilities Viau et al. CR-Kp colonization can also trigger a clonal outbreak and newly colonized patients can develop fatal infections Snitkin et al.
Risk factors for colonization and infection with antibiotic-resistant K. Risk factors associated with ESBL colonization and infection include prior treatment with antibiotics, prolonged hospitalization, prolonged ICU stay, and mechanical ventilation Jacoby, ; Lautenbach et al. Risk factors associated with carbapenem-resistant K. As with endemic strains of K.
Though antibiotic-resistant strains can infect an array of body sites similar to endemic strains, they frequently cause UTIs Selden et al. This may represent inoculation of the urinary tract with K.
In the s and s, reports began to emerge from the Asian Pacific Rim detailing severe infections due to K. These infections were unique in that they were community-acquired CA , a departure from the classic presentation of K. Common infections due to these hypervirulent K. Symptoms of PLA vary between individuals and are frequently non-specific. Diagnosis requires radiographic imaging Johannsen et al.
The incidence of PLA rose sharply in Taiwan, from Patient risk factors for severe infection with hvKP include being aged 55—60 years, male, and having diabetes mellitus Lee et al. Throughout China there is a high prevalence of hvKP strains among K. Reported mortality rates 14—30 days vary among patients in Asia who are infected with hvKP 4. Alarmingly, these strains have begun to emerge worldwide, including in the United States Lederman and Crum, ; Nadasy et al.
Fortunately, hvKP isolates are typically highly susceptible to most antibiotics Fang et al. Recently, however, an outbreak due to a carbapenem-resistant ST11 hvKP isolate occurred in China, heralding the potential for dual-risk isolates that both cause severe infections and are increasingly difficult to treat or are fatal due to antibiotic resistance Gu et al.
The most striking aspect of hvKP isolates is their ability to cause severe infections in otherwise healthy patients. This severity is attributed to virulence factors encoded by the accessory genome.
This phenotype has been determined to be conferred by two proteins: RmpA, which regulates capsule production Hsu et al. Capsule types K1 and K2 are also highly associated with hvKP and may play a more important role in virulence than rmpA and magA Yeh et al. They are also often sequence type 23 ST23 a phylogroup strongly associated with the K1 capsule type Liu et al.
The siderophore Ybt has also been associated with hypervirulent strains Holt et al. Furthermore, the siderophore Aer has been distinguished as the most common siderophore secreted by hypervirulent K. Allantoin has been identified as a source of nitrogen in various bacterial species and as both a nitrogen source and a carbon source in K. Allantoin is a metabolic intermediate of purine degradation by various organisms including microbes Vogels and Van der Drift, An allantoin utilization operon has been associated with hypervirulent K.
Deletion of a regulator gene in the operon corresponds to decreased virulence in a mouse model, indicating that the ability to use as a nitrogen source increases virulence in K.
Allantoin metabolism genes are variably encoded chromosomally in K. PFGE typing of liver and fecal isolates from patients with PLA demonstrates little or no differences within patients but discernable differences between patients. But each of these strains may have colonized many people, as a random sampling of fecal isolates from asymptomatic patients revealed some of the same PFGE types seen in PLA isolates Fung et al. These findings suggest that, similar to opportunistic K.
If colonization is a potential reservoir for infection with hvKP strains, then understanding the community carriage rates is important. With that in mind, a recent study sought to identify the fecal carriage rate of K1 K. They determined that 4. Of these, The overall K. They further determined that the K1 carriage rate was higher in foreigners who lived in Korea compared to those of Korean descent who lived outside of Korea A similar study was undertaken where stool isolates from healthy Chinese adults living in various Asian countries were collected over 6 years and tested for the presence of K.
It was determined that 9. Rates were similar for Chinese living in all countries tested except Thailand and Vietnam. Strikingly, the overall K. These findings establish that hvKP can be a significant proportion of K. The most obvious concern about K. With treatment options already limited, this result could be devastating. These isolates will cause severe disease but will be difficult or impossible to treat. Genomic analyses of strains worldwide have already detected the convergence of hypervirulence and carbapenemase genes in a number of isolates Bialek-Davenet et al.
These isolates had acquired portions of the hypervirulent virulence plasmid pLVPK, and contained several virulence factors associated with hypervirulent strains including genes encoding the siderophore Aer and the mucoid phenotype regulator gene rmpA.
Alarmingly, no antibiotics were effective in treating the infections caused by these hv CRE K. The ST11 strains identified in this study also included genes encoding the siderophore Ybt. These CRE K. Improved molecular epidemiology and sequencing capabilities have recently demonstrated that isolates frequently identified as K. Although initially distinguished by variations in their core genome, these species can also be separated by the content of their accessory genome Holt et al.
As three distinct species, these groups may vary in their epidemiology of colonization and infection. Not much is known about the least frequently isolated of the three Kp phylogroups, K. The most common sites of K. Klebsiella variicola was proposed as a new, distinct species based on both genetic and biochemical differences from K.
A consistent trait of K. Genes responsible for nitrogen fixation, such as those in the nif operon, can be considered part of the core genome of K. While colonization of plants is common, colonization rates in humans is unknown. Though this species is associated with environmental sources, the clinical importance of K. In fact, a recent study determined that patients with bloodstream infections due to K. This increased mortality was not due to any known virulence factors and was significant after controlling for patient co-morbidities, suggesting that K.
Since it is only relatively recently that these species have been differentiated, there is a paucity of information in the literature regarding colonization rates and virulence factors in K.
Along with K. Indeed, genetic exchange across these three species can occur Holt et al. Though classically considered an opportunistic, hospital-acquired pathogen that infects only immunocompromised hosts, two additional types of K. Across these three types, intestinal colonization rates are significant and serve as a reservoir for isolates capable of causing infection.
For hospital-onset infections, the association between colonization and subsequent infection is established and strong. And for all types of K. Understanding colonization and infection as two distinct stages with potentially varying risk factors will further aid in understanding the pathogenesis of K.
The accessory genome is likely critical in determining the differences in infection risk and outcomes of endemic, antibiotic-resistant, and hypervirulent K.
Several K. Furthermore, most studies involving K. While understanding of pathogenesis for each distinct type is important, a broad understanding of how K. These species may have distinct epidemiological and resistance profiles based on the composition of their accessory genome. However, it is becoming evident that there is a reservoir of genes that are exchanged and assembled to create strains with varying infectious and antibiotic-resistant potential Figure 1.
Therefore, it is increasingly clear that Klebsiella can assemble a large accessory genome from a larger pool of available genes to determine their ability to colonize, infect, and resist antibiotics in humans. Figure 1. Klebsiella pneumoniae, variicola , and quasipneumoniae are three species that share a pool of accessory genes. The combination of genes in the accessory genome differs between species and pathotypes within K.
These accessory genes can also combine to form new pathotypes hvCRE and can be shared across species. Enterobactin Ent, blue and Fimbriae dark green represent conserved genes; accessory genes are shown as examples and are not a definitive list. The evolutionary tree is not drawn to scale. RM and MB: conceived design of the review, drafted, and critically revised the work, and provided final approval for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Thank you to Nicholas W. Lukacs, Harry L. Snitkin for reading an early draft of the review. Abraham, E. An enzyme from bacteria able to destroy penicillin.
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Dorman, M. Klebsiella pneumoniae : when a colonizer turns bad. Fang, C. Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Farida, H. Bacteremia needs to be treated right away, as these infections can progress to sepsis and septic shock , which can turn deadly. A UTI can affect any part of the urinary system, including the urethra, kidneys, bladder, and ureters.
Symptoms include a strong, frequent need to urinate, burning sensation during urination, pelvic pain, and cloudy, bloody, or strong-smelling urine. Women are at a greater risk of getting a UTI than men. Wound and surgical site infections If K. Typically, this happens with wounds caused by injury or after surgery. Symptoms can include fever, blisters, fatigue, and pain at the wound or surgical site. Meningitis Bacterial meningitis can occur when pneumoniae enters the membranes surrounding the brain and spinal cord.
It is a very serious infection that can be life-threatening. The bacteria can cause the tissues around the brain to swell, interfering with blood flow. This can result in paralysis or stroke. Symptoms, including high fever, headaches, and stiff neck, come on quickly, usually within 24 hours of infection.
If left untreated, bacterial meningitis can lead to death. A study published in the American Journal of Medicine estimated the overall annual population incidence of klebsiella infection is 7. The researchers found elderly people and men were at highest risk of infection. According to the National Institutes of Health Genetic and Rare Diseases Information Center, klebsiella is responsible for 8 percent of all hospital-acquired infections.
Furthermore, a CDC report found carbapenem -resistant klebsiella is responsible for about 7, infections and deaths each year. Some strains of E. According to the CDC, carbapenem-resistant E. Editorial Sources and Fact-Checking.
Klebsiella Infection. Klebsiella Pneumoniae in Healthcare Settings. Centers for Disease Control and Prevention. November 24, Klebsiella Pneumonia. March 25, Journal of Thoracic Disease. September
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