1. Introduction

Avian pathogenic Escherichia coli (APEC), an extra-intestinal pathogenic E. coli (ExPEC), causes diverse local and systemic infections in poultry, including chickens, turkeys, ducks, and many other avian species [1]. The most common infections caused by APEC in chickens are perihepatitis, airsacculitis, pericarditis, egg peritonitis, salphingitis, coligranuloma, omphalitis, cellulitis, and osteomyelitis/arthritis; these are commonly referred as avian colibacillosis [2]. APEC also causes swollen head syndrome in chickens and osteomyelitis complex in turkeys [2]. Colibacillosis is one of the leading causes of mortality (up to 20%) and morbidity in poultry and also results in decreased meat (2% decline in live weight, 2.7% deterioration in feed conversion ratio) and egg production (up to 20%), decreased hatching rates, and increased condemnation of carcasses (up to 43%) at slaughter [1,3,4]. Furthermore, APEC is responsible for high mortality (up to 53.5%) in young chickens [4]. Taken together, along with the treatment expenses, APEC costs the poultry industry hundreds of millions of dollars in economic losses worldwide [5]. In the United States (US), it has been estimated that economic losses to the broiler industry can be as high as $40 million annually only due to carcass condemnations [6].

APEC can affect all species of poultry in all types of production systems [3]. APEC is also prevalent (9.52% to 36.73%) in all age groups of chickens [7]. Broiler chickens between the ages of 4 and 6 weeks are more susceptible [1], whereas layer chickens can be affected by APEC throughout the grow and lay periods, particularly around the peak egg production and late lay period [1]. In the US, it is estimated that at least 30% of commercial flocks are affected by APEC at any point of time [8]. Multiple APEC serotypes have been associated with colibacillosis cases in the field outbreaks; however, three serotypes (O78, O2, and O1) account for the majority (more than 80%) of the cases [1,5]. APEC leads to systemic infections in chickens either as a primary pathogen or secondary to viral [infectious bronchitis (IBV), Newcastle disease (NDV), avian influenza (AIV)] and Mycoplasma (Mycoplasma gallisepticum (MG) infections, immunosuppressive disease [(infectious bursal disease (IBD)], or environmental stresses (overcrowding, high level of dust and ammonia) by entering through oral and respiratory routes [1,5]. Interestingly, studies have shown that APEC can colonize the gastrointestinal and respiratory tracts of chickens without causing disease and only translocate to extra-intestinal sites in the presence of stressors (production-related stress, immunosuppression, and concurrent infections) as an opportunistic pathogen [2,9]. APEC invades the gastrointestinal and respiratory tracts through abraded tracheal and intestinal epithelium in the presence of stressors and reaches bloodstream and internal organs [1,2,3]. Chickens get infected through contaminated feed and water and can spread to other birds through the feco-oral or aerosol route [1,2,3]. Furthermore, APEC can be vertically transmitted from infected breeders via contaminated eggs [1,2,3]. An overview of APEC infection in chickens is shown in Scheme 1.

APEC utilizes different virulence and pathogenesis factors to cause disease in chickens, primarily adhesins, invasins, protectins, iron acquisition systems, and toxins [2]. These factors facilitate adhesion, invasion, evasion from the host immune responses, colonization, proliferation, and systemic dissemination of APEC, thereby allowing the establishment of infection in chickens [2]. In addition to these factors, several other bacterial factors including but not limited to secretion systems (type III and VI), quorum sensing (QS) system, transcriptional regulators, two-component systems, and metabolism-associated genes also contribute to APEC pathogenesis in chickens [10,11,12,13,14,15,16,17,18]. An in-depth understanding of these factors and their roles in APEC pathogenesis will help to develop new effective preventative and therapeutic treatments.

Recent studies suggest APEC (particularly isolates belonging to sequence types ST95 and ST131 or O1, O2, and O18 serogroups) as a potential foodborne zoonotic pathogen as well as a source or reservoir of extra-intestinal infections in humans [4,19,20,21]. Particularly, APEC shares genetic similarity with human ExPECs, uropathogenic E. coli (UPEC), and neonatal meningitis E. coli (NMEC), and possesses UPEC-and NMEC-defining virulence genes with the ability to cause urinary tract infections (UTI) and meningitis in mice and rat models [4,22]. Furthermore, the detection of APEC-specific ColV (colicin V) plasmids in human ExPEC isolates suggests a possible zoonotic transmission of APEC from poultry to humans [21]. Therefore, APEC is a pathogen of importance to the poultry industry and public health.

Antibiotics (tetracyclines, sulfonamides, and aminoglycosides) are frequently used to control colibacillosis in chickens [23]. However, increasing resistance of APEC to different classes of antibiotics, including medically important antibiotics (β-lactams, colistin, and carbapenems), suggests challenges ahead in using antibiotics to control APEC infections in chickens [24]. Furthermore, there is no effective vaccine available to protect chickens against APEC infections, which is mainly due to the diversity of APEC serotypes associated with colibacillosis cases in the field outbreaks [5]. Currently, only two vaccines (live-attenuated APEC O78 ΔaroA Poulvac^® E. coli vaccine and inactivated Nobilis^® E. coli vaccine containing F11 fimbrial and FT flagellar antigens) are commercially available for use in chickens [5,25]. These scenarios necessitate the development of new and alternative therapies to control APEC infections in chickens. Probiotics, bacteriophages, and different new therapies (innate immune stimulants, growth and QS inhibitors, and antimicrobial peptides) have shown promising efficacy in reducing APEC infections in chickens [26,27,28,29,30]; however, none of these have advanced into field applications to date.

This entry is adapted from the peer-reviewed paper 10.3390/pathogens10040467