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Pathogens are a group of micro-organisms or parasites that can invade a host and cause disease, and derive their name from the Greek words 'pathos' and 'genesis'. These tiny organisms range in size from micron-sized bacteria to nano-sized viruses and, although invisible to the naked eye, can pose a wide range of health threats by releasing toxins, destroying host cells, or hijacking metabolic systems. According to the World Health Organisation (WHO), the transmission of pathogens requires three main elements: a source of infection, a mode of transmission, and a susceptible population. It is worth noting that not all microbes are harmful - around 90% of microbes in the human body, such as gut probiotics, maintain a symbiotic relationship with the host and are involved in key physiological processes such as digestion and immune regulation.
The study of pathogens has been carried out throughout the history of human civilization: the Black Death of the 14th century, caused by the bubonic plague bacillus, decimated the European population by a third and led to the beginnings of the modern public health system; and the COVID-19 pandemic of 2019 highlighted the speed at which infectious diseases spread in an era of globalization and the complexity of prevention and control. According to The Lancet 2022 study, antibiotic resistance directly contributes to 1.27 million deaths per year, a number that is projected to exceed ten million by 2050. These figures not only highlight the destructive power of pathogens, but also the need for continued research: from understanding disease mechanisms to developing new therapies, the human-pathogen game has always been a central driver of medical progress.
To cater to research needs, CD Genomics offers a suite of advanced pathogen detection technologies. Their wide array of products includes specialized NGS panels designed for pathogen detection, such as the Pathogens Detection Panel, which can accurately identify various infectious pathogens. This technology is crucial in understanding the genetic makeup of pathogens and developing targeted treatment strategies. Moreover, CD Genomics' HBV/HPV/EBV Capture Sequencing provide valuable insights into low-abundance viruses, supporting researchers in advancing scientific discoveries and disease management strategies.
Pathogen categories at a glance: From bacteria, molecular machines with double lives and alarming antimicrobial resistance, to viruses, evolutionary masters of host manipulation and rapid adaptation, explore the intricate world of microbial pathogens.
Bacteria: double agents in the microcosm
As unicellular prokaryotes, bacteria are widely distributed in the natural environment and their pathogenicity depends on the interaction of virulence factors with host immunity. Some strains cause disease by releasing toxins, such as the enterotoxin secreted by Staphylococcus aureus, which can cause severe vomiting and diarrhea, and the neurotoxin produced by Mycobacterium tetani, which can cause tonic muscle spasms with a mortality rate of up to 20-30%. Other bacteria directly destroy host tissues, such as Mycobacterium tuberculosis, which forms caseous necrotic lesions in the lungs, and Helicobacter pylori, which causes ulcers and even gastric cancer by eroding the stomach lining. In addition, Neisseria gonorrhoeae evades antibody recognition through antigenic variation, and Streptococcus pneumoniae resists phagocytosis by using polysaccharide capsules, immune escape mechanisms that make the infection process more insidious.
Antibiotic resistance increases the threat of bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) is completely resistant to β-lactam antibiotics, and carbapenem-resistant Enterobacteriaceae are considered a 'top priority threat' by the WHO. In 2016, the first superbug resistant to the MCR-1 gene-mediated polymyxin, which acts as the last line of antibiotic defense, was discovered in the US, and the findings ring alarm bells for the post-antibiotic era. According to the Lancet 2022 study, global deaths from drug-resistant bacterial infections have surpassed those from malaria and AIDS combined, underscoring the severity of the problem.
Neisseria gonorrhoeae evades antibody recognition through antigenic variation (Yee et al., 2023)
Viruses: evolutionary masters of host manipulation
Viruses are composed of nucleic acids (DNA or RNA) and protein capsids and depend on host cells to complete their replication cycle. Influenza viruses are spread by droplet transmission and kill 290-650,000 people worldwide each year; hepatitis B viruses (HBV) are transmitted through blood or body fluids and can develop into cirrhosis or even liver cancer in the long term; dengue viruses, transmitted by mosquito bites in the tropics, cause 390 million infections each year. The specificity of viruses lies in their evolutionary strategies: the new coronavirus variant Omicron BA.1 has more than 30 mutations in its spiking protein, which significantly increases its ability to evade the immune system; herpes simplex viruses can remain latent in the ganglia for long periods and reactivate when the host's immunity wanes; avian influenza viruses (H5N1) have gained the ability to transmit across species through genetic recombination and have become a potential pandemic agent.
Viruses vary widely in their incubation period and transmission efficiency. For example, the Ebola virus has a short incubation period (2-21 days) but is up to 90% lethal, while the human papillomavirus (HPV) can cause cervical cancer decades after persistent infection. According to a 2020 study in the journal Science, viruses and their hosts have a co-evolutionary history spanning hundreds of millions of years, with about 8% of the human genome derived from ancient retroviral integration events. This deep genetic entanglement suggests that it is neither practical nor necessary to completely eradicate certain viruses, and that a dynamic equilibrium is key.
Immunity and attack experiments with the new coronavirus Omicronjon (Wang et al., 2024)
Fungi and parasites: underappreciated pathogens
Fungal infections can be classified as either superficial or invasive. Candida albicans often causes thrush, a white patch on the oral mucosa, while Cryptococcus neoformans can penetrate the blood-brain barrier and cause deadly meningitis, especially in HIV-infected people. The CDC has classified Candida ear as an 'urgent threat' because it is more than 90% resistant to triazole antifungals and can survive for long periods in hospital environments. In 2019, an outbreak of Candida ear infections in a New York hospital led to the death of 40% of infected patients within 90 days, highlighting the difficulty of preventing and controlling it.
Parasites complete transmission through complex life cycles. Plasmodium enters the human body through the bite of Anopheles mosquitoes, causing 241 million infections annually; Schistosoma haematobium larvae penetrate the human skin after being released from freshwater snails, causing hepatosplenomegaly and portal hypertension; and scabies mites tunnel through the stratum corneum of the skin, causing severe itching and secondary infections. These parasitic diseases are particularly prevalent in areas with poor sanitation, and according to the WHO, approximately 2.4 billion people worldwide are at risk of parasitic infections. Remarkably, some parasites have developed strategies to manipulate host behaviour - Toxoplasma gondii infects rats by removing their fear of cat urine, increasing the likelihood of entering the food chain.
Innate immune signaling and the influence of parasite effectors (Zhao et al., 2020)
Pathogens not only cause individual diseases, but they also change the way society functions. Acute infections such as cholera can lead to dehydration shock within hours, while the association of chronic infections (e.g. EBV) with nasopharyngeal cancer and lymphoma was confirmed by a 2019 study in the journal Nature. Certain pathogens damage the host indirectly through immune cross-reactivity - streptococcal infections are followed by antibodies that mistakenly attack the heart valves, triggering rheumatic heart disease - and such sequelae continue to be a major burden in the developing world. In India, for example, there are around 300,000-350,000 new cases of rheumatic heart disease each year, 40-50 percent of which are in children.
The socio-economic impact is also profound. In the United States, the direct cost of treating drug-resistant bacterial infections is US$20 billion a year, and dengue costs Southeast Asian countries US$1.3 billion in GDP.During the 2014 Ebola epidemic in West Africa, the collapse of health systems led to a spike in mortality from malaria, tuberculosis and other common diseases, creating a "cascade of disasters". A 2015 study by The Lancet found that nearly 80 percent of Ebola survivors were traumatized by social discrimination, highlighting the deep damage infectious diseases can do to the human fabric. The more subtle effects are cultural: fear of the Black Death in medieval Europe gave rise to the artistic theme of the 'dance of death', while contemporary mask culture has reshaped social etiquette.
Humans must abandon the 'absolute sterilisation' mentality and re-establish the symbiotic relationship with pathogens by maintaining the balance of the microbiome (e.g. rational use of antibiotics, use of probiotics), vaccination (e.g. HPV vaccine significantly reduces the risk of cervical cancer) and the use of nanopore sequencing technology to achieve precise traceability.
Reconstructing the cognitive framework
First, the myth of 'absolute sterilisation' must be discarded. The balance of the human microbiome is essential for health: excessive use of antibiotics can lead to gut dysbiosis, increasing the risk of allergies and metabolic diseases. Several studies have shown that about 30% of depressed patients have gut dysbiosis, suggesting a potential role for the 'gut-brain axis' in neuropsychiatric disorders. Second, vaccine research and development continues to rewrite the history of the disease - since the introduction of universal HPV vaccination in Australia in 2007, the incidence of cervical cancer in women under 25 has fallen by 77% and precancerous lesions by 90%. Finally, precision medicine is providing new tools for prevention and control, such as nanopore sequencing technology, which can quickly target pathogen transmission chains and is the basis for the 2021 Beijing New Crown Traceability.
Multi-layered prevention and control system
Personal protection must go back to the basics: proper hand washing and rubbing for at least 20 seconds can reduce the risk of respiratory infections by 20-40%. Fermented foods, such as yoghurt, help maintain probiotic homeostasis. At the healthcare level, China needs to improve antibiotic misuse and promote antimicrobial stewardship. The antibiotic prescription rate in China's primary care remains high at 52.9% (2014-2018 data), far exceeding the WHO recommended limit of 30%. In terms of global collaboration, the ONE Health initiative integrates human, animal and environmental health surveillance, with successes including the rapid containment of H7N9 avian influenza in 2013 and the effective interruption of the chain of cross-species transmission in the 2019 Ebola outbreak in Congo. Phage therapy and CRISPR gene-editing technologies have successfully removed latent viral reservoirs from HIV-infected cells in the laboratory, providing new ideas for curing AIDS.
Future technology outlook
With the development of synthetic biology, scientists are trying to create 'artificial phage libraries' to combat drug-resistant bacteria. In 2022, a team from the Massachusetts Institute of Technology (MIT) developed an engineered phage that can attack three types of drug-resistant bacteria simultaneously, and animal experiments have shown that its efficiency in clearing infections reaches 98%. In the field of vaccines, mRNA technology is expanding from new core vaccines to transform malaria control. These breakthroughs herald a new phase as humanity moves from passive defense to active intervention.
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