Streptococcus pneumoniae (S. pneumoniae) has a multifaceted bond with its human host and causing several diseases in children and adults when host flexible immunity and bacterial acquisition factors allow them to invade essentially sterile spots, such as the middle ear spaces (causes otitis media), lungs (causes pneumonia), bloodstream (causes sepsis) and meninges (causes meningitis). In the early 1940s, management of pneumococcal infections used to be somewhat straightforward, and penicillin commonly was the antibiotic of choice. Soon after mainstreaming antibiotic usage, worldwide emergence of antibiotic resistance among S. pneumoniae isolates has changed this approach. Multiple factors, like prior antibiotic use, inappropriate usage of antibiotics especially in young age, and day care attendance are the most commonly identified risk features for the spread of penicillin resistance and other multiple-antibiotic resistance. Basic fundamental mechanisms of most pneumococcal resistances have been identified, several organizations like WHO, CDC, BSAC, EUCAST started campaigns for appropriate antibiotic use and also the introduction of pneumococcal conjugate vaccines have been recommended to limit the further emergence and spread of pneumococcal resistant.
- drug-resistant S. pneumoniae
- World Health Organization
- upper respiratory tract
- β-lactam antibiotics
- penicillin-binding proteins
According to WHO, bacterial resistance to antibiotic drugs are now one of the most global events that threaten humanity; due to new resistant mechanisms acquired by bacteria that help them to evade both natural and chemical elimination systems that are, immune system and antibiotic drugs . With the ability to acquire resistance, simple infections can create major clinical problems for different patients, leading to serious events that include death. Unfortunately, although warnings about the aimless use of antibiotic drugs have been made by medical experts since the 1940s, the expenditure of antibiotic drugs are still increasing . This issue is not only related to certain countries like India and South Africa where antibiotics are available without prescriptions, but also worldwide . This implies that restricted guidelines must be made by specialized health sectors in both hospitals and pharmacies. Not only that but also generating a public awareness forum where people around the world are educated about the dangerousness of misusing antibiotic drugs. However, if increased consumption of antibiotics continues, doors for bacteria are going to be open, permitting them to enter an adaptive phase where mutations and among other things can take place; leading to deleterious consequences . Indeed, the world today must reform the way antibiotics are being prescribed and utilized; not doing so, will impose a fast-rising threat which can be slowed down if certain behavior changes like a simple hand washing are applied . Nevertheless, researchers in this field are facing a wide range of challenges which led to a major decrease in the discovery and development of new antibiotics; due to the widespread use of these drugs which have led to difficult new resistant bacteria families to appear . This can be illustrated by looking back in time, for instance, approximately 47 new antibiotics were developed collectively in the period from 1983 to 2002, while from 2003 to 2012 almost seven new drugs only were developed . This shows how close we are to reaching a post-antibiotic era where fear and trepidation from the simplest injuries and common infections are once again established. Therefore, the science community must come together and set up a focused system where only life-threatening resistant bacterium is targeted in order to safe major resources and develop better outcomes.
On one hand, we should also not forget to monitor and adjust the public behavior towards this topic, as it is the major fuel to this crisis. On the other hand, if this threat is left without a serious action, an estimation of nearly 10 million people will die every year in 2050 due to antimicrobial resistance, not to mention the huge cost burden with over 100 trillion USD . In this chapter, we aim to establish a comprehensive understanding of defense mechanism of certain worrying and life-threatening bacteria (
2. Insights into antimicrobial emergence
It is well-known to scientists that bacteria are one of cleverest creatures that can not only generate new methods continuously to evade the immune system and antibiotic drugs, but also adapt to various situations to ensure its survival and growth. By knowing that, it is important to explore their mechanism in an attempt to have a better understanding of how they work and function. However, it would make sense to direct all efforts to certain worrying bacteria that are resistant by prioritizing it according to certain criteria. To do so, WHO has published a global priority list of resistant bacteria to antibiotic drugs in order to facilitate a path that will guide researchers all around the world where the urgency of finding new treatments is vital . With the help of expert opinion and evidence-based data WHO-global priority pathogens list developed a multi-criteria decision analysis (MCDA) technique for prioritizing the research and development of new and effective antibiotic treatments. Following steps has been taken to set prioritization: (1) selection of antibiotic-resistant bacteria to be prioritized; (2) selection of criteria for prioritization; (3) data extraction and synthesis; (4) scoring of alternatives and weighting of criteria by experts; and (5) finalization of the ranking of pathogens. This list was created with the help of specialists all around the world and contains 12 most dangerous resistant bacteria families organized based on where exigency of new treatments is needed. The first three were sat as a
Furthermore, to face a great challenge like bacterial resistance a one must have a tremendous knowledge about their defense mechanism and the way they behave towards facing obstacles that are immune system and antibiotic drugs, and we attempt to review the accessible evidence and asses the relative importance of pathogens, and the status of drug-resistance
3. Streptococcus pneumoniae
3.1 Classification, transmission, colonization and invasion
3.2 Identified risk features of
Over the last 15 years,
3.3 Mechanisms of antimicrobial resistance
An organism is considered resistant when its growth
Antimicrobial resistance probably originated from horizontal resistance gene between bacterial species. These genes are acquired rapidly by the mechanism of plasmid promoted-conjugation, transformation or virus-induced transduction process, that all process contribute to the development of antimicrobial resistance. Due to these mechanisms some of the genes are inherited, some change to random DNA mutations in bacteria, and others are imported from related or distant bacteria  (Figure 3). Repeatedly use of antibiotic has been shown to be the strongest risk factor for the carriage and spread of resistant pneumococci, at both the individual and the community levels . Evidence showed that antimicrobial resistance developed in
Antibiotics have been a basis of pneumococcal disease treatment and either by decreasing or eradicating the bacterial load from host body . As production of penicillin started in the mid-1940s, after that treatment of pneumococcal infections has relied heavily upon penicillin and other β-lactam antibiotics, which showed most effective antibiotics against this bacterium. In 1912, a first antimicrobial-resistant pneumococcal infections were documented when optochin resistance in experimental mice was described . Five years later acquired optochin resistance was seen in humans . In 1967, the first clinical isolate in a pediatric patient in Australia reported with reduced penicillin susceptibility . During the period of 1970–1980, pneumococci resistant to penicillin, erythromycin, and trimethoprim-sulfamethoxazole (TMP-SMX) spread rapidly globally, including many developed nations . Tetracycline, chloramphenicol and fluoroquinolone resistances were also documented at relatively low levels compared to those for the above-mentioned antibiotics . More than 40% of isolates are penicillin resistant in several countries that lack significant conjugate vaccine coverage [40, 41]. Only few studies have been conducted on the acquisition of multidrug resistance however, these studies have found that extremes of age (i.e., <5 years and more than 65 years of age), previous use of β-lactam antibiotics by patients with noninvasive disease, antibiotic use in the last month by patients with nasopharyngeal colonization, population density, geographic location, and pneumococcal seven-valent conjugate vaccine (PCV7) serotype are all independent risk factors .
Typical therapy for the treatment of pneumococci disease (including invasive) are β-lactam antibiotics (benzylpenicillin, amoxicillin or ampicillin). Soon after mainstreaming antibiotic usage, multi-resistant pneumococcal clones emerged and disseminated worldwide. Penicillin resistant
Another cause of β-lactam resistance is due to phenotypic expression of penicillin resistance alterations that results in modification of penicillin-binding proteins (PBPs), consequently reducing peptidoglycan synthesis. This loose affinity causes cell lysis and bacterial cell death . As peptidoglycan serves important roles in maintenance of cell integrity, cell expansion, cell division, cellular diffusion and surface anchoring. Gram positive bacterium pneumococcal peptidoglycan is composed of alternating glucosamine and
Six PBPs genes have been described in
As discussed earlier, PBP genes (
With the advent of more advanced laboratory techniques, including whole-genome sequencing, and continued, high-quality surveillance of antimicrobial resistance, we can continue to further expand our understanding of this area. Special program and campaigns run by various organization like, WHO, CDC, BSAC, EUCAST should continue to be in all countries to decrease not only the burden of disease but also antimicrobial-resistant pneumococci. Also more focus on pneumococcal conjugate-vaccines because the new conjugate vaccines target these resistant serotypes, the implementation of use of these vaccines is expected to have an important role in limiting the spread of antibiotics-resistant
Conflict of interest
The author declares that there is no conflict of interest.