Klebsiella pneumoniae (KP) is a common Gram-negative bacillus in nature, which can cause multiple systemic infections and is also a common pathogen of human infection. With the large-scale use of antibiotics, the emergence of antibiotic resistance and drug-resistant strains has gradually become a thorny problem in clinical practice. Attempts have been made to solve these problems by developing vaccines to prevent and control Klebsiella pneumoniae infection.

In 1882, Carl Friedlander first extracted and described Klebsiella pneumoniae from the lungs of patients with pneumonia. KP is a Gram-negative bacillus belonging to the family Enterobacteriaceae, which is widely found in nature. KP is facultative anaerobic without flagella and spores requiring, which has low nutritional requirements large colonies when growing on common medium. KP is mucus-like, easy to pull into silk by inoculation ring, whose features help identification, and make it capable to be made into capsules. According to its virulence and pathogenic characteristics, KP can be divided into common Klebsiella pneumoniae (cKP) and high-virulence Klebsiella pneumoniae (hvKP), of which hvKP is more likely to cause health and youth population due to its high mucus. Studies have found that hvKP mainly causes community-acquired liver abscess, meningitis, severe pneumonia, endophthalmitis, etc., and that how far it can be spread. The specific causes and mechanisms of this phenomenon are still unclear.

As is known, KP can cause a variety of infections, such as lung infections, urinary tract infections, abdominal infections, surgical site infections and even bloodstream infections, and patients with severe underlying diseases and immune dysfunction are more susceptible to the infection of the pathogen, which occurs in the distribution of infection departments, including neonatal wards, ICU, geriatric wards, urology wards, etc.ICU is the key clinical department of KP infection, which accounts for about 15% of ICU Gram-negative infections. The study has shown that KP ranks second among the pathogens causing Gram-negative bacteremia and urinary tract infections, and is the most common pathogen causing respiratory infections in hospitals. The mortality rate of KP is extremely high. According to statistics, the death rate of bloodstream infection caused by KP is 20% to 30%, and the total is 1.3/100,000, of which the KP bacteremia and pneumonia is up to more than 50%.

At present, the abuse of broad-spectrum antibiotics in the clinic makes KPincreasingly resistant to antibiotics. An epidemiological study on KP resistance in 2018 showed that the resistance rates of KP isolates to aztreonam and ceftazidime reached 55.4% and 55.7%, respectively. KP resistance mechanisms are complex and diverse, including β-lactamase production, aminoglycoside inactivating enzymes, chromosomal variation, plasmid and integron mediated, outer membrane porin deletion, target position change, biofilm formation and active efflux mechanism wait. As the proportion of KP infections in clinical infections continues to increase, people are also trying to focus on immunotherapy while studying new treatment options or new effective drugs to control infections. Many scholars have begun to try to use the immunogenicity of different structures of KP, such as KP whole bacteria, ribosomes, outer membrane proteins, capsular polysaccharides, lipopolysaccharide, etc., to induce the body to produce anti-KP immunity, so as to prevent or control KP infection. The types of Klebsiella pneumoniae vaccines are as follows:

1. KP inactivated whole vaccine (IWC)

IWC uses physical heating or chemical substances such as formalin and formaldehyde to inactivate pathogenic microorganisms, and then induces the body's immune response with inactivated pathogens to prevent infection. IWC has not been used in clinical practice due to the endotoxicity and safety of some of the pathogens themselves. In 2013, Sun et al. prepared a KP inactivated whole-bacteria vaccine, but found that the sitA protein carried by KP has obvious toxic effects on cells. sitA is a ferrous and manganese ion involved in the transport of its own nutrient metabolism in Enterobacteriaceae bacteria. A regulatory transporter gene whose expression level changes as the culture conditions of the bacteria change. In the study, Sun et al. used genetic engineering techniques and demonstrated in vivo and in vitro experiments that the loss of sitA will attenuate the toxicity of KP bacteria. They deactivated the sitA deletion strain and the wild strain by ultraviolet light, and then injected it into the peritoneal cavity of the mouse. Two weeks later, the mice were intraperitoneally infected with the same dose of the wild type strain, and it was found that all the mice injected with the strain of the hitA survived. The survival rate of the control group was 80%, and the difference was statistically significant. The results of this study showed that the inactivated strain of sitA deletion strain can effectively induce the immune function of mice, which can retain its good immunogenicity and eliminate the toxicity of sitA. Therefore, knock out the sitA to construct the avirulent strain of KP. It is necessary to carry out more in-depth research on the vaccine. In addition to IWC, another relatively safe technique is to use a complete lysate method of bacterial cells to make a non-cellular vaccine containing all cellular components. However, cell lysates of KP can cause severe local reactions at the site of inoculation, often leading to necrosis of skin tissue and, in severe cases, even anaphylactic shock. This phenomenon indicates that KP lysate contains a variety of toxic components harmful to the body. Simple lysis without selective rejection can not be applied to the body for induction of immunity, but KP bacteria have complex components and various protein structures. The selective elimination of research work can be huge and lengthy. Therefore, there are few related studies in this area in recent years.

To be continued in Part Two…